tbuckley/cabot-search huggingface dataset:
Abstract A25: Transcriptional control of inflammatory signaling in the megakaryocyte and erythroid lineages
Authors: Bon Q. Trinh, Nicolas Barengo, Sang Bae Kim, Ju-Seog Lee, Patrick A. Zweidler-McKay, Honami Naora
Journal: Cancer Research (2016)

Abstract Thrombocytosis, characterized by high platelet counts, and anemia, caused by low numbers of red blood cells, are associated with poor outcomes in solid tumors and occur in several types of myeloid disorders. The megakaryocyte and erythroid lineages give rise to platelets and red blood cells, respectively, but the mechanisms that cause increased megakaryopoiesis and concurrently decreased erythropoiesis are poorly understood. In this study, we identified that expression of DLX4, a transcription factor encoded by a homeobox gene, increases during megakaryopoiesis and decreases during erythropoiesis. Overexpression and knockdown experiments using normal CD34+ stem/progenitor cells and bipotent K562 cells demonstrated that DLX4 induces lineage markers and morphologic features of megakaryocytes, and concomitantly represses erythroid marker expression and hemoglobin levels. Gene Ontology and Gene Set Enrichment Analyses of genome-wide changes in gene expression induced by DLX4 showed that DLX4 induces a megakaryocytic transcriptional program and inhibits an erythroid transcriptional program. Bioinformatic analysis also revealed that DLX4 induces gene signatures that are associated with NF-kappaB signaling. The ability of DLX4 to promote megakaryocyte development and to inhibit erythroid differentiation was diminished by blocking NF-kappaB activity or by repressing IL1B, a transcriptional target of DLX4. These findings indicate that DLX4 promotes megakaryocyte development at the expense of erythroid generation in part by inducing inflammatory signaling. Studies are ongoing to investigate the transcriptional control by homeobox genes of inflammatory signaling in thrombocytosis and anemia that are associated with solid tumors and myeloproliferative diseases. Citation Format: Bon Q. Trinh, Nicolas Barengo, Sang Bae Kim, Ju-Seog Lee, Patrick A. Zweidler-McKay, Honami Naora. Transcriptional control of inflammatory signaling in the megakaryocyte and erythroid lineages. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A25.
Case-Control Study: Smoking History Affects the Production of Tumor Antigen–Specific Antibodies NY-ESO-1 in Patients with Lung Cancer in Comparison with Cancer Disease–Free Group
Authors: Dagmar Myšíková, Irena Adkins, Nad'a Hradilová, Ondřej Palata, Jan Šimonek, Jiří Pozniak, Jan Kolařík, Anna Skallová-Fialová, Radek Špíšek, Robert Lischke
Journal: Journal of Thoracic Oncology (2016)

Lung cancer is the leading cause of cancer mortality worldwide; therefore, understanding the biological or clinical role of tumor-associated antigens and autoantibodies is of eminent interest for designing antitumor immunotherapeutic strategies.Here we prospectively analyzed the serum frequencies of New York esophageal squamous cell carcinoma 1 (NY-ESO-1), human epidermal growth factor 2/neu, and melanoma-associated antigen A4 (MAGE-A4) antibodies and expression of the corresponding antigens in tumors of 121 patients with NSCLC undergoing an operation without prior neoadjuvant chemotherapy and compared them with those in 57 control age-matched patients with no history of a malignant disease.We found that only antibodies specific for NY-ESO-1 (19.8% [n = 24 of 121]) were significantly increased in the group of patients with NSCLC compared with in the controls. NY-ESO-1 seropositivity was significantly positively associated with an active smoking history in patients with NSCLC but not in smokers from the control group. In tumors, the frequency of NY-ESO-1 mRNA expression was 6.3% (in four of 64 patients), the frequency of human epidermal growth factor 2/neu (HER 2/neu) expression was 11.9% (five of 42), and the frequency of MAGE-A4 expression was 35.1% (20 of 57). MAGE-A4 expression in tumors correlated with smoking status and male sex in patients with NSCLC. Patients with squamous cell carcinoma displayed higher expression of NY-ESO-1 and MAGE-A4 in tumors than did patients with adenocarcinoma. On the other hand, 94.7% of nonsmoking patients in our study had adenocarcinoma (of whom 73.7% were women).These results confirm the reported high immunogenicity of NY-ESO-1 and suggest that a smoking-induced chronic inflammatory state might potentiate the development of NY-ESO-1-specific immune responses. Moreover, smoking might contribute to the expression of other cancer/testis antigens such as MAGE-A4 at early stages of NSCLC development.
New discriminatory serum protein profiles in breast cancer patients
Authors: M.-C. Gast, J. Bonfrer, E. Rutgers, J. Schellens, J. Beijnen
Journal: Journal of Clinical Oncology (2004)

574 Background: The sensitivity and specificity of the currently used biomarkers to diagnose breast cancer are not optimal. This study aimed to develop and validate an assay that identifies new, discriminatory serum protein profiles in breast cancer patients. Methods: We analyzed sera of 140 pre- and postmenopausal breast cancer patients (samples taken prior to therapy, BC) and 110 age matched healthy controls (HC), using Ciphergen's ProteinChip® Surface Enhanced Laser Desorption Ionisation Time-Of-Flight Mass Spectrometry system. Patients had stage I-III disease, tumors were positive or negative for Her2, estrogen and progesteron receptors. Several array chemistries were tested. With the array type that distinguished best between BC and HC, the 250 samples, divided into 3 groups (A: 54 BC, 24 HC, B: 39 BC, 39 HC and C: 47 BC, 47 HC) were analyzed. The Biomarker Patterns Software constructed a decision tree with the data from each group. The trees were prospectively validated with the data from the other groups. Influence of relevant demographic co-variables on the discrimination between BC and HC was also explored. Results: Optimum discrimination was achieved using an IMAC30 array. Analysis of the data generated revealed >20 significant mass-to-charge ratios (m/z), with which several trees were constructed. A representative tree, constructed with the data from group A, is based on the intensities of m/z 3090 and 8940 Da. Results of the prospective validation of this tree are presented in the table. Conclusions: This study demonstrated that breast cancer patients, with diverse demographic and tumor biochemical characteristics and tumor stage, exhibit a distinctive protein profile in comparison with healthy controls. The ultimate goal of this study is to identify these proteins, as this will give us insight into the pathogenesis of breast cancer and possible new leads for the development of new therapies and strategies for diagnosis. No significant financial relationships to disclose.
Acute Megakaryoblastic Leukemia in Childhood: Comparison Between Patients with and without Down Syndrome
Authors: Maria Sara Felice, Jorge Gabriel Rossi, Marta Gallego, Cristina N. Alonso, Silvia Eandi Eberle, Myriam Ruth Guitter, Patricia L. Rubio, Elizabeth M Alfaro, Cristian Sanchez La Rosa, Pedro Zubizarreta
Journal: Blood (2014)
Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma
Authors: James J. Hsieh, David Chen, Patricia I. Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S. Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H. Huberman, Umesh Bhanot, Michael S. Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H. Won, Daoqi You, Agnes Viale, William Lee, A. Ari Hakimi, Michael F. Berger, Nicholas D. Socci, Emily H. Cheng, Jennifer Knox, Martin H. Voss, Maurizio Voi, Robert J. Motzer
Journal: European Urology (2016)
Efficacy and Safety of Salvage Therapy Using Carfilzomib for Relapsed or Refractory Multiple Myeloma Patients: A Multicentre Retrospective Observational Study
Authors: Eli Muchtar, Moshe Gatt, Ory Rouvio, Chezi Ganzel, Evgeni Chubar, Celia Suriu, Tamar Tadmor, Olga Shevetz, Noa Lavi, Tzippy Shochat, Yael C Cohen, Irit Avivi, Pia Raanani, Hila Magen
Journal: Blood (2015)
High Affinity Binding of FVIII to VWF Is Not Required for the Haemostatic Effect of FVIII In Vivo
Authors: Heidi L Holmberg, Marianne Kjalke, Ditte Karpf, Ida Hilden, Hermann Pelzer, Mikael Koefoed-Hansen, Laust Johnsen, Lars Thim, Johan Karlsson, Christina Jespersgaard, Gert Bolt, Henning Stennicke
Journal: Blood (2011)
Severe winter asthma exacerbations can be prevented by omalizumab, but there is no carryover effect
Authors: Peter D. Sly, Julie Varghese, Farhana Noor, Mimi L.K. Tang, Ingrid Laing, Steve Oo, Franciska Prastanti, Peter N. LeSouef, Patrick G. Holt
Journal: Journal of Allergy and Clinical Immunology (2016)
MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis
Authors: Yingmei Wang, Limei Hu, Ping Ji, Fei Teng, Wenyan Tian, Yuexin Liu, David Cogdell, Jinsong Liu, Anil K. Sood, Russell Broaddus, Fengxia Xue, Wei Zhang
Journal: Journal of Hematology & Oncology (2016)

Endometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP) gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. Immunohistochemistry was used to measure MIIP expression in normal and EC tissue. Both gain-of-function (infection) and loss-of-function (siRNA) assays were used to alter MIIP expression levels. The effect of MIIP on cell migration and invasion was measured by transwell assay. F-actin immunofluorescence staining was used to observe the cell morphology. The activation of GTP-loaded Rac1 was evaluated by Rac activity assay kit. Immunoprecipitation/WB was used to measure the interaction between MIIP and PAK1. We demonstrate that MIIP expression was significantly decreased in EC patients comparing to the normal ones, and decreased MIIP expression in EC tissues is associated with deep myometrial invasion, advanced stage, and the presence of lymph node metastasis. Using both gain-of-function (infection) and loss-of-function (siRNA) assays, we show that MIIP markedly blocked EC cell migration, whereas loss of MIIP led to increase in EC cell migration. We demonstrate that elevated expression of MIIP resulted in cytoskeleton reorganization with decreased formation of lamellipodia. We also provide evidence that MIIP is a key molecule in directing Rac1 signaling cascades in EC. Ectopically expressed MIIP consistently competed with Rac1-GTP for binding with the PAK1 p21-binding domain. Our data show that MIIP and PAK1 bind each other and that a C-terminal polyproline domain of MIIP is required for PAK1 binding. Deletion of the PAK1-binding domain of MIIP reduced cell migration-inhibiting activity. MIIP may function as a tumor suppressor gene for endometrial carcinoma. MIIP attenuates Rac1 signaling through a protein interaction network, and loss of this regulator may contribute to EC metastasis.
An imaging study of vemurafenib in patients with BRAFV600-mutated metastatic melanoma.
Authors: Secondo Lastoria, Antonio M Grimaldi, Luigi Aloj, Ester Simeone, Anna Romano, Corradina Caraco, Marcello Curvietto, Assunta Esposito, Corrado Caraco, Nicola Mozzillo, Valter Torri, Paolo Antonio Ascierto
Journal: Journal of Clinical Oncology (2012)

e19034 Background: Targeted therapy against the mutated form of BRAF V600 is a proven effective therapy for melanoma. Objective of this exploratory study was to describe the change over time of PET-scan results and verify the association of PET-scan examination with the objective response (OR) (defined by RECIST criteria) in melanoma pts treated with vemurafenib. These preliminary results reported here regards the description of changes over time of PET-scan. Methods: Patients treated with vemurafenib at our institution were considered eligible. Patients were evaluated with PET-scan at baseline and at day 7, 15 and 30 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (mean SUV x lesion volume) were recorded and compared for single lesions in the 4 exams. Differences between each PET-scan performed during therapy and baseline were calculated and coded as yes/no response basing on predefined criteria. Association of PET responses and achievement of OR were estimated by means of logistic regression models. Odds ratio and C statistics were used to define strength of association and discriminant capability. C statistics obtained with PET/CT at different timepoints were compared. Results: As of January 2012, 7 out of 20 required pts have been enrolled. A total of 48 lesions were available for evaluation. A reduction in lesion SUVmax and TLG values compared to baseline was evident in all the post-therapy studies (reduction in SUV max at day 7 – 51 ± 28 %, day 14 – 67 ± 24 % and day 30 –69 ± 29 %, reduction in TLG at day 7 – 41 ± 83 %, day 14 – 69 ± 35 % and day 30 – 68 ± 37 %). A comparison of the day 15 and day 30 studies showed essentially stable uptake values (SUV max variation -3 ± 41 %, TLG 5 ± 56 %). However, 14/23 lesions in 3 patients showed increased SUV max and TLG values between the day 15 and day 30 studies likely indicating early signs of treatment resistance. Conclusions: Our preliminary results suggest that PET/CT may be an early surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation.
Proceedings of the 2016 China Cancer Immunotherapy Workshop
Authors: Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li, Zihai Li, Lieping Chen, Edward B. Garon, Siwen Hu-Lieskovan, Wei Ding, Chong-Xian Pan, Weijing Sun, Yong-Jun Liu, Lei Zheng, Delong Liu, Michel Sadelain, Cassian Yee, Rongfu Wang, Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han, Lisa H. Butterfield, Timothy A. Chan, Wenru Song, Ruirong Yuan, Bo Lu, Ke Liu, Max Ning, Harald Enzmann, Heinz Zwierzina
Journal: Journal of Hematology & Oncology (2016)

A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina
Signatures of Archaic Adaptive Introgression in Present-Day Human Populations
Authors: Fernando Racimo, Davide Marnetto, Emilia Huerta-Sánchez
Journal: Molecular Biology and Evolution (2016)

Comparisons of DNA from archaic and modern humans show that these groups interbred, and in some cases received an evolutionary advantage from doing so. This process-adaptive introgression-may lead to a faster rate of adaptation than is predicted from models with mutation and selection alone. Within the last couple of years, a series of studies have identified regions of the genome that are likely examples of adaptive introgression. In many cases, once a region was ascertained as being introgressed, commonly used statistics based on both haplotype as well as allele frequency information were employed to test for positive selection. Introgression by itself, however, changes both the haplotype structure and the distribution of allele frequencies, thus confounding traditional tests for detecting positive selection. Therefore, patterns generated by introgression alone may lead to false inferences of positive selection. Here we explore models involving both introgression and positive selection to investigate the behavior of various statistics under adaptive introgression. In particular, we find that the number and allelic frequencies of sites that are uniquely shared between archaic humans and specific present-day populations are particularly useful for detecting adaptive introgression. We then examine the 1000 Genomes dataset to characterize the landscape of uniquely shared archaic alleles in human populations. Finally, we identify regions that were likely subject to adaptive introgression and discuss some of the most promising candidate genes located in these regions.
What is the optimal strategy to confirm the diagnosis of epithelial ovarian carcinoma (EOC) prior to neoadjuvant chemotherapy (NAC)?
Authors: J. E. Dodge, H. Mackay, S. Klachook, M. Bernardini, P. Shaw, K. J. Murphy, E. Lo, B. P. Rosen, O. Freedman
Journal: Journal of Clinical Oncology (2009)

5511 Background: NAC has been increasingly utilized in clinical practice yet no standard diagnostic strategy has been defined for EOC prior to the administration of NAC. We reviewed the diagnostic process for patients receiving NAC at our centre to determine if an optimal diagnostic strategy could be determined. Methods: A retrospective chart review of all patients known to receive NAC followed by cytoreductive surgery for presumed EOC between 1994 and 2007 was performed. Diagnostic strategies were defined as histology, cytology, and clinical. Performance of these strategies in predicting final pathology, based on expert pathology review of surgery specimens, was compared using Fisher's exact test. Results: 152 patients were included. Initial diagnosis was made on the basis of: cytology (paracentesis/thoracentesis)- 89 (59%); percutaneous biopsy- 40 (26%), radiology and CA-125–18 (12%), surgical biopsy -5 (3%). The final diagnosis was consistent with invasive EOC in 145 patients (95%). The remaining 7 were ovarian LMP (4), ovarian carcinosarcoma (1), endometrial serous cancer (1), and GI tumor (1). The diagnostic accuracies of the 3 strategies differed: histology (43/45), cytology (87/89), and clinical (15/18), p = 0.039. 17% of patients had an alternate final diagnosis when clinical parameters were the only basis for the diagnosis of EOC prior to NAC. A specific EOC subtype was identified pre-op in 82 patients (histology-31 cases, cytology-51 cases). Subtype differed between pre- and post-treatment samples in 13% of histology and 8% of cytology cases. Conclusions: Diagnosis of EOC based on cytology or histology-based strategies are superior to clinical factors alone. Even in a centre with trained gynecologic cytopathologists, cytology and biopsy strategies preclude accurate subtype diagnosis in a significant number of patients. These data are important for clinical practice and the design of future clinical trials. No significant financial relationships to disclose.
GW26-e0740 Safety and Efficacy of IntraCoronary Hypoxia-precondItioned Bone Marrow MonoNuclear Cell Administration for Acute Myocardial Infarction Patients: The CHINA-AMI Randomized Controlled Trial
Authors: Xinyang Hu, Xin Huang, Qian Yang, Lihua Wang, Jianzhong Sun, Hongwei Zhan, Jianjing Lin, Zhaoxia Pu, Jun Jiang, Yong Sun, Meixiang Xiang, Xianbao Liu, Xiaojie Xie, Xia Yu, Zexin Chen
Journal: Journal of the American College of Cardiology (2015)
Chronic Myeloid Leukemia with Variant t(9;22) Shows Dysregulated Expression of Genes Included in Pivotal Cellular Pathways
Authors: Francesco Albano, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Luciana Impera, Giuseppina Tota, Antonella Russo Rossi, Crescenzio Francesco Minervini, Angela Minervini, Paola Casieri, Giorgina Specchia
Journal: Blood (2012)
Safety of maintenance bevacizumab after first-line chemotherapy for advanced ovarian and müllerian cancers
Authors: S. M. Campos, D. S. Dizon, S. A. Cannistra, M. Roche, C. N. Krasner, S. T. Berlin, N. S. Horowitz, P. DiSilvestro, U. A. Matulonis, R. T. Penson
Journal: Journal of Clinical Oncology (2007)

5517 Background: Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes VEGF, but is associated with arterial complications and GI perforations in patients with advanced ovarian cancer. Maintenance antiangiogenic therapy is an attractive strategy for patients after first line therapy. However, no data exist on the safety of maintenance bevacizumab in this setting. Methods: An open label phase II clinical trial of carboplatin, paclitaxel and bevacizumab (CPB) in newly diagnosed patients =ECOG 2, with chemotherapy naïve, stage =IC, epithelial müllerian tumors. Patients receive carboplatin AUC 5 IV, paclitaxel 175 mg/m 2 IV, and bevacizumab 15 mg/kg IV for 6–8 cycles D1 Q21. Bevacizumab is omitted in the first cycle, and continued as single agent for one year. Results: 58 patients are evaluable. Median age is 58 (18–77), and 39(67%) were ECOG 1. 43(74%) have ovarian, 8(14%) uterine papillary serous (UPSC) tumors, 4(7%) peritoneal, and 3(5%) fallopian tube cancers. 38(65%) were serous, 8(14%) MMMT, 4(7%) clear cell, and 3(5%) endometrioid cancers (5(9%) mixed/other). 36(62%) were stage III and 11(19%) stage IV. Surgery was optimal in 45(80%) patients. 50 patients have completed chemotherapy, associated with 2 PEs, and 2 GI perforations, all occurring during the induction chemotherapy phase of treatment. 43 patients have received 360 cycles of maintenance therapy with mild toxicity. 6(14%) have come off for PD, 4(9%) for toxicity (inc. 1 nasal perforation), 4 withdrew consent, and 3 patients asymptomatic, continue despite a rising CA125. During maintenance there has been no grade IV toxicity, and 13 grade III toxicities (musculoskeletal pain (5), dyspnea, hyperglycemia, hypertension (1 grade III, 4 grade II), infection, lymphopenia, thrombocytopenia, proteinuria, syncope). Radiographic responses were documented in 21 of 28 (75%: CR 11, PR 10). Median PFS is 11(1–21) months at 13 months median FU. Conclusion: Maintenance bevacizumab is feasible and well tolerated with mild myalgias, and hypertension common but treatable side effects. No significant financial relationships to disclose.