tbuckley/cabot-search huggingface dataset:
Abstract 5286: Expression of cancer type amino acid transporter LAT1 is a prognosis prediction factor in breast carcinoma: comparison between triple-negative and non-triple-negative types
Authors: Masaaki Ichinoe, Tetsuo Mikami, Kiyomi Hana, Nobuyuki Yanagisawa, Hitoshi Endou, Isao Okayasu, Yoshiki Murakumo
Journal: Cancer Research (2015)

Abstract Purpose: Amino acid transporters play important roles in cell survival and proliferation. L-Type amino acid transporter 1 (LAT1) is one of the major Na+-independent neutral amino acid transporters. LAT1 has an aspect of oncofetal protein. Recently, high levels of LAT1 expression have been reported in various tumors, such as prostate cancer, pancreas cancer, bile duct cancer, lung cancer and stomach cancer.We revealed LAT1 expression is an independent prognosis marker in stomach cancer, prostate cancer and pancreas cancer. The purpose of the present study was to investigate the LAT1 expression in breast carcinoma and relationship between LAT1 expression and prognosis. Materials &amp; Methods: We enrolled 290 patients with invasive breast carcinoma surgically resected between 2006 and 2010 at Kitasato University Hospital and Toho University Omori Medical Center, Japan. We investigated LAT1 expression in the enrolled breast carcinoma cases by immunohistochemical staining. All cases were divided into two groups, 78 cases of triple negative carcinoma (TNBC) and 212 cases of non-triple negative carcinoma (NTNBC), with immunohistochemistry of estrogen and progesterone receptors and Her2. After LAT1 expression was compared between TNBC and NTNBC, correlations among LAT1 expression, Ki-67 labeling index (LI), CD98 expression, and clinicopathological findings was assessed. Results: TNBC showed significantly higher LAT1 expression than NTNBC. TNBC also showed significantly higher CD98 expression rather than NTNBC. LAT1 expression of extraductal invasive cancer cells was significantly higher than those of intraductal carcinoma cells. A significantly positive correlation was observed between LAT1 expression and CD98 expression. Further, a positive correlation between LAT1 expression and Ki-67 LI was found. Log-rank test in overall breast cancers revealed that high LAT1 expression group showed significantly poor prognosis, compared to low LAT1 group. In NTNBC, high LAT1expression cases possessed poorer prognosis than low LAT1 expression cases. Conclusion: In invasive ductal carcinoma of breast, LAT1 expression has a potential for a prognosis prediction factor. LAT1 offers a potential target for anti-cancer therapy by its inhibitor JPH203 which has been developed by us. Citation Format: Masaaki Ichinoe, Tetsuo Mikami, Kiyomi Hana, Nobuyuki Yanagisawa, Hitoshi Endou, Isao Okayasu, Yoshiki Murakumo. Expression of cancer type amino acid transporter LAT1 is a prognosis prediction factor in breast carcinoma: comparison between triple-negative and non-triple-negative types. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2015-5286
In Vitro Induction of Myeloid Leukemia Specific CD4 and CD8 T-Cells by CD40 Ligand Activated B Cells Gene-Modified to Express Primary Granule Proteins.
Authors: Hiroshi Fujiwara, Joseph J. Melenhorst, Frank El Ouriaghli, Sachiko Kajigaya, Matthias Grube, Giuseppe Sconocchia, Katayoun Rezvani, David A. Price, Nancy F. Hensel, Daniel C. Douek, A. John Barrett
Journal: Blood (2004)
Abstract 1897: Metformin as a chemoprevention agent for lung squamous cancer
Authors: Michael K. Asiedu, Matthew R. Barron, Marie Christine Aubry, Dennis Wigle
Journal: Cancer Research (2015)

Abstract Background: Squamous cell carcinoma is a common type of lung cancer and accounts for about 25-30% of all non-small cell lung cancers. Metformin is a drug commonly prescribed as first-line treatment for type-2 diabetes, with some evidence showing that the drug can also act directly on cancer cells. One of the mechanisms of action is through activation of the AMP-activated protein kinase (AMPK) which is involved in control of energy homeostasis in cells. The goal of this study was to determine metformin response in different cell lines and different cellular contexts, and to use that information to work towards the generation of a metformin “sensitivity index” that could be used guide individualized chemoprevention. Methods: We performed cell survival analysis on squamous cell carcinoma lines, skin fibroblast lines and differentiated IPS cell lines to identify differences in metformin response both for different cell lines and for cells in different cell context. Microarray profiling was used to determine differentially expressed genes that are regulated by metformin treatment in order to generate signatures of metformin response. Results: Cell survival analysis showed that different cell lines respond differently to metformin, and cells of identical genotypes in a variety of differentiated states or cellular contexts also show differential response to metformin. Gene expression profiling of metformin treated cells identified differentially expressed genes that may mediate metformin response. Conclusion: Differences in response to metformin treatment across a variety of cell lines and cellular contexts suggest heterogeneity that may be patient-specific. Using genes that are differentially expressed following metformin treatment, we identified a 55-gene set that can be used as a metformin “sensitivity index” to stratify patients into metformin responders and non-responders and guide individualized chemoprevention. Citation Format: Michael K. Asiedu, Matthew R. Barron, Marie Christine Aubry, Dennis Wigle. Metformin as a chemoprevention agent for lung squamous cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1897. doi:10.1158/1538-7445.AM2015-1897
Falls in hospice: analysis of the problem through the method of clinical audit
Authors: A. Affatato, L. D'alessandro, M. Solaroli, S. Marani, G. Pasini, F. Alessandrini, M.C. Monterubbianesi, A. Marzaloni, P. Tomasello, D. Tassinari
Journal: Annals of Oncology (2015)
Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer
Authors: Michela Capello, Leonidas E. Bantis, Ghislaine Scelo, Yang Zhao, Peng Li, Dilsher S. Dhillon, Nikul J. Patel, Deepali L. Kundnani, Hong Wang, James L. Abbruzzese, Anirban Maitra, Margaret A. Tempero, Randall Brand, Lenka Brennan, Eleonora Feng, Ivana Taguchi, Vladimir Janout, Matthew A. Firpo, Sean J. Mulvihill, Matthew H. Katz, Samir M. Hanash
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Methods: Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Results: Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set). Conclusion: The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.
Professor Neil B. Pride (1931–2016)
Authors: Peter J. Barnes
Journal: European Respiratory Journal (2017)

He was a respiratory physiologist who made major contributions in the field of lung mechanics, which helped to explain the mechanisms of airway narrowing in common lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD).Neil was one of the first to do research in COPD, probing its underlying mechanisms and helping us to understand how treatments work.His scientific output dealt with the mechanics of every aspect of the respiratory system, from the nose to the diaphragm, including coughing.He was an outstanding intellect, who not only knew respiratory physiology better than anyone else, but was also knowledgeable about many other areas outside his own research field.He was extraordinarily well-read and had an amazing memory, never seeming to forget anything that he had heard.He was a gifted teacher, able to simplify and communicate complex ideas in lung physiology, and he was a doctor much loved by his patients.For all his brilliance, he was a modest, generous person and an inspiring mentor to young researchers.His writing was as clear as his talks and he published many very influential papers, reviews, chapters and books.
Abstract 1227: Differential efficacy of p53 restoration in induction and maintenance of senescence in premalignant and malignant cells
Authors: Mohammad Harajly, Hassan Zalzali, Sandra Ghayad, Farrah Ghamloush, Mark Jabbour, Hussein Basma, Ayman Tawil, Zafar Nawaz, Raya H. Saab
Journal: Cancer Research (2015)

Abstract Restoration of p53 in tumors has been suggested as a possible therapeutic approach, based on preclinical in vivo and in vitro evidence of possible efficacy. However, the relationship between the timing of p53 restoration and its efficacy is still unclear. We now show that restoration of p53 in murine pre-malignant proliferating pineal tumors results in effective cell cycle exit and induction of cellular senescence, while p53 reactivation in established malignant pineal tumors does not impact cell proliferation, unless paired with DNA damaging therapies. This differential effect was not related to levels of p19Arf expression, as its expression was more pronounced in malignant tumors, nor to MAPK pathway activity. Interestingly, in premalignant lesions induced to senesce by p53 restoration, inactivation of p53 after senescence resulted in re-entry into the cell cycle, and rapid tumor progression. These findings were also validated in cell culture models of Cyclin D1-induced and RasV12-induced senescence in murine pineal cells and mouse embryo fibroblasts, respectively. Evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET), of which pineoblastoma is a subtype, showed low activity of the p53 pathway, while only one of 6 tumors had p53 deletion or mutation. Together, this data shows that restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, where it may need to be paired with DNA damaging agents, to engage it in tumor suppression. Furthermore, p53 activation may need to be continually sustained for effective tumor suppression in such lesions undergoing senescence as a tumor suppressor mechanism. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene seems to be intact but the pathway inactive in the majority of examined tumors. Citation Format: Mohammad Harajly, Hassan Zalzali, Sandra Ghayad, Farrah Ghamloush, Mark Jabbour, Hussein Basma, Ayman Tawil, Zafar Nawaz, Raya H. Saab. Differential efficacy of p53 restoration in induction and maintenance of senescence in premalignant and malignant cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1227. doi:10.1158/1538-7445.AM2015-1227
Complete remission (CR) during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs)
Authors: D. Santini, M. Santoni, A. Conti, G. Procopio, E. Verzoni, L. Galli, G. Di Lorenzo, U. De Giorgi, D. De Lisi, M. Nicodemo, M. Maruzzo, F. Massari, S. Buti, E. Biasco, R. Ricotta, C. Porta, B. Vincenzi, P. Marchetti, S. Cascinu, G. Tonini
Journal: Annals of Oncology (2015)
Combination of PP1/PP2 and LY294002 Induce Apoptosis Efficiently to TEL-FGFR3 Transfected Ba/F3 Cells.
Authors: Daisuke Okamura, Fumiharu Yagasaki, Tomoya Maeda, Maho Ishikawa, Itsurou Jinnai, Masami Bessho
Journal: Blood (2005)
Abstract 1116: Oncogene signatures identify novel therapeutic targets and combinatorial strategies in breast cancer
Authors: Stephen Guest, Zachary Kratche, Jonathan Irish, Aliccia Bollig-Fischer, Elizabeth Garrett-Mayer, Stephen Ethier
Journal: Cancer Research (2015)

Abstract During the course of tumorigenesis, cancer cells acquire a large number of genetic and epigenetic alterations. A subset of these alterations results in the generation of driver oncogenes that play critical roles in initiating and maintaining the transformed phenotype. We hypothesize that most solid tumors are simultaneously driven by multiple driver oncogenes that together form an oncogene network and that durable therapies for solid tumors will need to target multiple oncogenes. Identifying multiple driver oncogenes from among the large number of mutated/amplified genes present in most solid tumors is a nontrivial task that will require novel approaches. In this work, we have combined genome-wide, RNAi-based dropout screens with copy number, expression and exome sequencing analysis to identify the full complement of driver oncogenes that function in a panel of breast cancer cell lines. The panel of cell lines used for this study is the SUM panel of breast cancer cells which contains 10 cell lines and includes representatives of HER2 positive, ER positive, and triple negative breast cancer subtypes. For each line we have identified multiple activated driver oncogenes that when combined define a complete oncogene signature for the cell line. All of the oncogene signatures contain both well-characterized oncogenes that are known to play a role in breast cancer as well as novel driver genes that do not have a well-characterized role in breast cancer. Subsequent work has confirmed the role of several of the novel driver oncogenes including the epigenetic modifier KAT6A and the apoptotic regulator BCL2L1. Additionally, we show that the cell line oncogene signatures can be used to successfully predict sensitivity of individual cell lines to small molecule inhibitors. Predictions of sensitivity to inhibitors were confirmed through the integration of oncogene signatures with published data from large-scale drug screens across numerous cancer cell lines. Finally, we demonstrate the utility of oncogene signatures through their use in the design of novel therapeutic strategies that effectively reduce cancer cell viability. Citation Format: Stephen Guest, Zachary Kratche, Jonathan Irish, Aliccia Bollig-Fischer, Elizabeth Garrett-Mayer, Stephen Ethier. Oncogene signatures identify novel therapeutic targets and combinatorial strategies in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1116. doi:10.1158/1538-7445.AM2015-1116
Abstract 1550: Significance of ectopic lymph node-like structures in neuroendocrine tumors of the small bowel
Authors: Mauro Cives, Jonathan Strosberg, Stacey A. Simons, Domenico Coppola
Journal: Cancer Research (2015)

Abstract The formation of extranodal tertiary lymphoid follicles and lymphoid cell aggregates has been described in nonmalignant conditions including autoimmune diseases and chronic inflammation as well as in cancer. Tumor-induced lymph node-like structures (LLS) participate in the host's antitumor immune response by driving intratumoral immune cell priming. We evaluated the host immune response by immunohistochemistry in 60 well differentiated small bowel NETs. A miRNA microarray analysis was also performed to identify a molecular signature of LLS presence. In 13/60 samples the immune response was organized as ectopic LLS. When present, LLS were localized at the invasive edge of the tumors and contained germinal centers in different stages of maturation. CD21+ dendritic cells were present within the follicular germinal centers, while CD3+ T cells were dispersed in the parafollicular cortex zone surrounding the CD20+ B cell area of the follicles. Time to progression of metastatic tumors was compared in an exploratory cohort of 5 patients with strong evidence of LLS vs 5 patients with no evidence of LLS and was substantially longer in the former group (94 vs 28 months; p = 0.15). Updated survival and miRNA microarray analysis will be presented at the meeting.The understanding of the functional nature of LLS may provide new insights into the pathogenesis of the disease, possibly furnishing a new tool for prognostic stratification and prediction of response to immune-based treatments. Citation Format: Mauro Cives, Jonathan Strosberg, Stacey A. Simons, Domenico Coppola. Significance of ectopic lymph node-like structures in neuroendocrine tumors of the small bowel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2015-1550
Abstract 3816: The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression
Authors: Bingnan Li, Xiaolu Zhang, Nick de Jonge, Magnus Björkholm, Dawei Xu
Journal: Cancer Research (2015)

Abstract DNA methyltransferase inhibitors (DNMTIs) such as 5-azacytidine (5-AZA) have been used for the treatment of acute myeloid leukemia (AML) and other malignancies, and inhibition of global/gene-specific DNA methylation is widely accepted as a key mechanism behind their anti-tumor activity. It is currently unclear whether other mechanisms are involved in DNMTI's action. Because telomerase or telomerase reverse transcriptase (TERT) plays a key role in malignant transformation and progression through telomere elongation and other telomere lengthening-independent activities, and TERT or telomerase has been shown to confer chemo- or radio-resistance to cancer cells, we determine whether DNMTIs affect telomere function and whether TERT/telomerase interferes with their anti-cancer efficacy. We showed that 5-AZA induced DNA damage and telomere dysfunction in AML cell lines by demonstrating the presence of 53-BP1 foci and the co-localization of 53-BP1 foci with telomere signals, respectively. Telomere dysfunction was coupled with diminished TERT expression, shorter telomere and apoptosis in 5-AZA-treated cells. However, 5-AZA treatment did not lead to changes in the methylation status of subtelomere regions. Downregulation of TERT expression similarly occurred in primary leukemic cells derived from AML patients exposed to 5-AZA. TERT over-expression significantly attenuated 5-AZAmediated DNA damage, telomere dysfunction and apoptosis of AML cells. Taken together, 5-AZA mediates the down-regulation of TERT expression, and induces telomere dysfunction,which consequently exerts an anti-tumor activity. These findings may have implications in DNMTI and telomerase-based strategies for cancer therapeutics. Citation Format: Bingnan Li, Xiaolu Zhang, Nick de Jonge, Magnus Björkholm, Dawei Xu. The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3816. doi:10.1158/1538-7445.AM2015-3816
610. An Inducible AAV Vector Mediating GDNF Signal Transduction at Clinically-Acceptable Sub-Antimicrobial Doxycycline Doses
Authors: Liliane Tenenbaum, Abdelwahed Chtarto, Marie Humbert-Claude, Olivier Bockstael, Atze T. Das, Sébastien Boutry, Ludivine Breger, Bep Claver, Robert N. Müller, Olivier De Witte, Marc Levivier, Cecilia Lundberg, Ben Berkhout
Journal: Molecular Therapy (2016)

Preclinical and clinical data stress the importance of pharmacologically-controlling glial cell line-derived neurotrophic factor (GDNF) intracerebral administration to treat Parkinson's disease. The main challenge is finding a combination of a genetic switch and a drug which, when administered at a clinically-approved dose, reaches the brain in sufficient amounts to induce a therapeutic effect. We describe a highly-sensitive doxycycline-inducible AAV vector (AAV-Dox-ON). This vector allowed for the first time a longitudinal analysis of inducible transgene expression in the brain using bioluminescence imaging. To evaluate the dose range of GDNF biological activity, AAV-Dox-ON-GDNF was injected in the rat striatum and increasing doxycycline doses administered orally. ERK signaling activation was induced at a plasmatic doxycycline concentration of 140 ng/ml which is known not to increase antibiotic-resistant microorganisms in patients. In these conditions, GDNF covered the majority of the striatum. No behavioral abnormalities or weight loss were observed. Motor asymmetry resulting from unilateral GDNF treatment only appeared with a 2.5-fold higher vector and a 13-fold higher inducer doses. Our data suggest that using our new sensitive doxycycline-inducible AAV vector, beneficial effects of GDNF can be obtained in response to sub-antimicrobial doxycycline doses without eliciting adverse effects.