tbuckley/cabot-search huggingface dataset:
CXCR4/SDF-1 Is a Key Regulator for Leukemia Migration and Homing to the BM: Impact of AMD3100 on In Vivo Response to Chemotherapy.
Authors: Bruno Nervi, Pablo Ramirez, Matthew Holt, Michael P. Rettig, Julie K. Ritchey, Julie L. Prior, David Piwnica-Worms, Gary Bridger, Timothy J. Ley, John F. DiPersio
Journal: Blood (2006)
Phenotypic and Prognostic Correlates of Spliceosome Mutations (SRSF2, SF3B1, U2AF35) in Chronic Myelomonocytic Leukemia with ≥ 1% Ring Sideroblasts.
Authors: Mrinal M. Patnaik, Terra L Lasho, Curtis A Hanson, Janice M Hodnefield, Ryan A Knudson, Rhett P Ketterling, Animesh Pardanani, Ayalew Tefferi
Journal: Blood (2012)
Abstract 304: Formation of uniform and reproducible 3D cancer spheroids in a high throughput plate format
Authors: Cindy Neeley, Chetana M. Revankar
Journal: Cancer Research (2015)

Abstract Cells grown on flat two dimensional (2D) tissue culture substrates can differ considerably from the three dimensional (3D) physiological environment. There is growing evidence that tumor cell aggregates or cancer spheroids are more representative of tumors in vivo and they exhibit several physiological traits including similar morphology, the formation of cell-cell contacts, decreased proliferation, increased survival rates and a hypoxic core. However, variability in cancer spheroid culture has been a persistent problem for researchers. This variability is linked to medium composition and volume, cell density, duration in culture, and most importantly, the cellular interactions with the culture dish itself. Here, we demonstrate that a hydrophilic polymer coated surface, Thermo Scientific Nunclon Sphera, inhibits cell attachment to the culture dish by blocking binding of the extracellular matrix (ECM). The U bottom wells in the Nunclon Sphera plate provide the ideal size and shape for single spheroid formation in each well, offering consistency and reproducibility to the 3D tumor model system in vitro. The growth of cancer spheroids in the Nunclon Sphera 96U-well plate is superior to that of the non-treated plate with less “satellite colonies” and faster cell aggregation at low seeding density. Cancer cell viability and spheroid health are also evaluated by fluorescence- and colorimetric- based assays in the Nunclon Sphera plates. The Nunclon Sphera 96U-well plate provides an excellent solution for reproducibly generating uniform 3D cancer spheroids that are suitable for many cell-based drug discovery procedures, co-culture studies, and high-throughput drug screening. Citation Format: Cindy Neeley, Chetana M. Revankar. Formation of uniform and reproducible 3D cancer spheroids in a high throughput plate format. [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 304. doi:10.1158/1538-7445.AM2015-304
Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment
Authors: Manar S. Shafat, Thomas Oellerich, Sebastian Mohr, Stephen D. Robinson, Dylan R. Edwards, Christopher R. Marlein, Rachel E. Piddock, Matthew Fenech, Lyubov Zaitseva, Amina Abdul-Aziz, Jeremy Turner, Johnathan A. Watkins, Matthew Lawes, Kristian M. Bowles, Stuart A. Rushworth
Journal: Blood (2017)
CBIO-41MutT HOMOLOG1 EXPRESSION IS UP-REGULATED IN MALIGNANT GLIOMA
Authors: Marco Timmer, Sara Kannampuzha, Roland Goldbrunner
Journal: Neuro-Oncology (2015)

INTRODUCTION: MutT homolog1 (MTH1) is required for the survival of cancer cells. Generally, cancer cells have irregular redox formation that result in production of reactive oxygen species, which damage the deoxynucleoside triphosphate pool and subsequent the DNA. MTH1 plays a crucial role by inhibiting the incorporation of oxidized bases into the DNA that avoid apoptosis of the cancer cells. Our aim was to analyze the pathophysiological role of MTH1 in glioma. METHODS: We analyzed the expression of MTH1 in surgical specimens of brain tumors of different WHO grades. Moreover, we compared primary and secondary glioblastomas, as well as tumors before and after chemotherapy. Western Blot, quantitative PCR, immunohisto- and immunocytochemistry were applied. RESULTS: Our work showed a significant higher level of MTH1 in brain tumor with higher WHO grade. Furthermore, patients treated with chemotherapy showed significantly lesser expression of MTH1. CONCLUSION: These results indicate that MTH1 might play an essential role in both, the malignization of glioma and disease progression in recurrent GBM. Inhibitors of MTH1 may develop towards targeted therapies in GBM.
491. Enhanced Delivery of Plasmid DNA to the Skin Using Gene Electrotransfer
Authors: Richard Heller, Amy Donate, Siqi Guo, Chelsea Edelblute, Anna Bulysheva
Journal: Molecular Therapy (2016)

The easy accessibility of skin makes it an excellent target for gene therapy applications. Gene electrotransfer (GET) of skin is a simple, direct, in vivo method to deliver genes for therapy and can be accomplished in a minimally invasive way. This approach has been tested in several animal models with varying skin thickness and delivery of plasmid DNA with GET resulted in significantly increased expression levels. Previously, we developed electrode arrays specifically for skin-based applications and designed applicators that can be easily applied and expanded. The limitations that we have encountered with our new designs are related to the depth of penetration of expression and occasionally cellular or tissue damage due to the required high applied voltage. GET requires a balance between efficient delivery and the maintenance of cell viability. In this current study, we have evaluated the addition of externally applied thermal energy to GET protocols to enhance delivery without increasing the applied voltage. We have determined both in vitro and in vivo that elevating the tissue temperature to between 42-45 0C was sufficient to enhance delivery when combined with GET. Administering GET to tissue with elevated temperature resulted in 5-8 fold higher expression compared to delivery with GET alone (ambient temperature). In addition, expression was obtained in the deep dermis and muscle utilizing a surface electrode. This deeper penetration was not consistently obtained when GET was used without a thermal component. Current work is evaluating approaches to achieve more uniform heat distribution within the tissue and to potentially elevate temperatures in specific areas of tissue in order to target gene expression. GET is a powerful tool that allows for manipulation of expression levels and kinetics. Adjusting the delivery parameters enables maximum control of the expression profile enhancing the potential for a successful therapeutic outcome. The addition of the thermal component allows further control of delivery and reduces the potential for cellular damage.
A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL
Authors: Oisin J. O’Connell, Francisco A. Almeida, Michael J. Simoff, Lonny Yarmus, Ray Lazarus, Benjamin Young, Yu Chen, Roy Semaan, Timothy M. Saettele, Joseph Cicenia, Harmeet Bedi, Corrine Kliment, Liang Li, Sonali Sethi, Javier Diaz-Mendoza, David Feller-Kopman, Juhee Song, Thomas Gildea, Hans Lee, Horiana B. Grosu, Michael Machuzak, Macarena Rodriguez-Vial, George A. Eapen, Carlos A. Jimenez, Roberto F. Casal, David E. Ost
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) in patients with non–small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies.Objectives: To develop a clinical prediction model for estimating the prN2/3.Methods: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1–3, N0–3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals.Measurements and Main Results: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography–computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82–0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85–0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132).Conclusions: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.
Heterodimeric IL15 Treatment Enhances Tumor Infiltration, Persistence, and Effector Functions of Adoptively Transferred Tumor-specific T Cells in the Absence of Lymphodepletion
Authors: Sinnie Sin Man Ng, Bethany A. Nagy, Shawn M. Jensen, Xintao Hu, Candido Alicea, Bernard A. Fox, Barbara K. Felber, Cristina Bergamaschi, George N. Pavlakis
Journal: Clinical Cancer Research (2016)

Purpose: Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer. Host lymphodepletion is associated with favorable ACT therapy outcomes, but it may cause detrimental effects in humans. We tested the hypothesis that IL15 administration enhances ACT in the absence of lymphodepletion. We previously showed that bioactive IL15 in vivo comprises a stable complex of the IL15 chain with the IL15 receptor alpha chain (IL15Rα), termed heterodimeric IL15 (hetIL15).Experimental Design: We evaluated the effects of the combination regimen ACT + hetIL15 in the absence of lymphodepletion by transferring melanoma-specific Pmel-1 T cells into B16 melanoma-bearing mice.Results: hetIL15 treatment delayed tumor growth by promoting infiltration and persistence of both adoptively transferred Pmel-1 cells and endogenous CD8+ T cells into the tumor. In contrast, persistence of Pmel-1 cells was severely reduced following irradiation in comparison with mice treated with hetIL15. Importantly, we found that hetIL15 treatment led to the preferential enrichment of Pmel-1 cells in B16 tumor sites in an antigen-dependent manner. Upon hetIL15 administration, tumor-infiltrating Pmel-1 cells showed a "nonexhausted" effector phenotype, characterized by increased IFNγ secretion, proliferation, and cytotoxic potential and low level of PD-1. hetIL15 treatment also resulted in an improved ratio of Pmel-1 to Treg in the tumor.Conclusions: hetIL15 administration improves the outcome of ACT in lymphoreplete hosts, a finding with significant implications for improving cell-based cancer immunotherapy strategies. Clin Cancer Res; 23(11); 2817-30. ©2016 AACR.
Durable Remission of Renal Cell Carcinoma After Donor Lymphocyte Infusion Is Unavoidably Linked with Graft Versus Host Disease As Illustrated by the Detection of Allo Reactive T Cells Recognizing a Novel Minor Histocompatibility Antigen Encoded by the FUCA2 Gene
Authors: Cornelis A.M. van Bergen, Elizabeth M.E. Verdegaal, Conny Hoogstraten, A.Q.M. Jeanne van Steijn, Linda de Quartel, Joan H. de Jong, Maaike Meyering, Marieke Griffioen, J.H.Frederik Falkenburg, Susanne Osanto
Journal: Blood (2012)
Increased Post-procedural Non-gastrointestinal Adverse Events After Outpatient Colonoscopy in High-risk Patients
Authors: David A. Johnson, David Lieberman, John M. Inadomi, Uri Ladabaum, Richard C. Becker, Seth A. Gross, Kristin L. Hood, Susan Kushins, Mark Pochapin, Douglas J. Robertson
Journal: Clinical Gastroenterology and Hepatology (2016)
Usefulness of Late Iodine Enhancement on Spectral CT in Acute Myocarditis
Authors: Claire Bouleti, Guillaume Baudry, Bernard Iung, Dimitri Arangalage, Jérémie Abtan, Gregory Ducrocq, Philippe-Gabriel Steg, Alec Vahanian, Marie-Cécile Henry-Feugeas, Nicoletta Pasi, Sylvie Chillon, Francesca Pitocco, Jean-Pierre Laissy, Phalla Ou
Journal: JACC. Cardiovascular imaging (2016)
Prognostic value of single nucleotide polymorphisms (SNPs) of candidate genes associated with inflammation in early-stage breast cancer.
Authors: J. L. Murray, P. Thompson, R. Zhou, S. Y. Yoo, Y. Liu, K. Do, A. A. Sahin, M. Bondy, A. M. Brewster
Journal: Journal of Clinical Oncology (2011)

1524 Background: Numerous studies have found little if any association between single nucleotide polymorphisms (SNPs) in genes associated with inflammation and breast cancer incidence. In contrast, the role of various inflammatory SNPs in predicting time to recurrence in early stage breast cancer (BC) patients has not been extensively examined. Methods: Genomic DNA from 1030 early stage BC patients was analyzed for 12 tagged SNPs of candidate genes involved in inflammation using the ILLUMINA Golden Gate platform. Cox proportional hazards models were used to evaluate the association between at risk alleles and breast cancer recurrence adjusted for clinical and pathologic covariates. Only SNPs with p values <0.1 were selected for the multivariable analysis using backward variable selection. Results: In univariable analyses 4 of 12 SNPs, NFKB1 (rs3774932), IL4(rs2243268), IL13(rs1800925) and IL10(rs1800896) were significantly associated with an increased time to recurrence (p< 0.1). In multivariable analyses NFkB (p = 0.02) and IL4 (p = 0.03) were independent predictors of longer time to recurrence compared to the dominant SNP when adjusted for stage, age and treatment. When number of at-risk alleles were counted for 4 significant SNPs, the presence of more risk alleles predicted for shorter disease free survival (Log-rank p value = 0.00079). Conclusions: These data suggest that individual and combined SNPs associated with inflammatory pathways are independent predictors of time to recurrence. This could have relevance towards the selection of drugs/immune modulators which targeting specific inflammatory pathways in an effort to prolong disease free survival in early stage BC patients.
The Brd-Inhibitor OTX015 Shows Pre-Clinical Activity in Anaplastic Large T-Cell Lymphoma (ALCL)
Authors: Michela Boi, Paola Bonetti, Maurilio Ponzoni, Maria Grazia Tibiletti, Anastasios Stathis, Esteban Cvitkovic, Giorgio Inghirami, Emanuele Zucca, Francesco Bertoni
Journal: Blood (2012)
Reply
Authors: Tammy T. Chang
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We thank Gortzen and Trebicka for their interest in our work.1 Studies suggest that mechanical force regulates RhoA mainly at the level of activity, by increasing the amount of activated guanosine triphosphate–bound RhoA, modulating guanine nucleotide exchange factors, and/or coupling guanosine triphosphate–RhoA to Rho‐kinase (ROCK).2 How RhoA mRNA expression affects the downstream effectors of the RhoA/ROCK pathway is less established. An interesting finding from our study is that there appears to be a threshold effect at the lower limit of fibrotic liver stiffness (1 kPa), at which point albumin production and hepatocyte nuclear factor 4α expression are inhibited.1 These results suggest that in determining the severity of hepatic dysfunction of a fibrotic liver, the gradient of stiffness in the liver tissue may be less important than the proportion of liver mass that reaches the threshold stiffness. We believe that the RhoA/ROCK pathway likely plays multiple cell type–specific roles that are important in modulating the progression and pathophysiology of liver fibrosis. In stellate cells, RhoA/ROCK activation may regulate fibrogenesis. In hepatocytes, as we have shown,1 RhoA/ROCK activation inhibits hepatocyte function in part through down‐regulation of hepatocyte nuclear factor 4α. The challenge for translating these discoveries into clinical therapies that benefit patients with liver fibrosis will be to identify efficacious RhoA or ROCK inhibitors that have minimal adverse systemic effects.5
Myelodysplasia-Related Changes Have Adverse Prognostic Significance in Children with Acute Myeloid Leukemia; A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).
Authors: Akitoshi Kinoshita, Hayato Miyachi, Hiromichi Matsushita, Miharu Yabe, Tomohiko Taki, Tomoyuki Watanabe, Akiko Saito, Daisuke Tomizawa, Nobutaka Kiyokawa, Takashi Taga, Takao Deguchi, Yoshiko Hashii, Kiminori Terui, Hiroyuki Takahashi, Yasuhide Hayashi, Akio Tawa, Keizo Horibe, Souichi Adachi
Journal: Blood (2012)
643. Enhanced Distribution of LCMV-Pesudotyped Bicistronic Lentiviral Vector Containing a Recombinant HSV-TK and EGFRwt for Glioblastoma Treatment
Authors: Jubayer A. Hossain, Kristoffer Riecken, Boris Fehse, Hrvoje Miletic
Journal: Molecular Therapy (2015)

Introduction: •Malignant gliomas, the largest group of primary intracerebral tumours, are one of the most difficult-to-cure cancers. The outcome has not improved significantly in the past years, despite considerable advances in our understanding of the molecular pathogenesis and the improvement of surgical techniques, radio- and chemotherapy. For glioblastoma multiforme (GBM), the most malignant form of glioma, the median survival time is generally less than one year.•Invasive glioma cells escape current therapies and are initiating recurrent tumors. Although complete remission of experimental GBM on MRI was observed, recurrent tumors came up which were frequently observed at different sites compared to the primary tumor 1. Thus invasive cells migrated to thes areas and initiated recurrent tumors.•The distribution of the therapeutic gene needs to be enhanced in order to target the invasive glioma cells and thereby improve the therapeutic effect and prolong the recurrence-free time window. By introducing EGFR, a gene that enhances invasion2, in addition to the suicide gene HSV-tk into our vector system, we want to improve the distribution of the therapeutic gene and also track invasive tumor cells. Key findings: •Expression of EGFR initiates an invasive program in transduced glioblastoma cells in vitro.•EGFR mediated infiltration of glioblastoma cells is retained in vivo in a rat xenograft model. [figure3 a &b]•The bicistronic lentiviral vector containing HSV-TK and EGFR [figure4] shows satisfactory cytotoxic profile in vitro. [figure5a & b] Conclusion: Expression of EGFR can enhance infiltrative nature of glioblastoma cells both in vitro and in vivo. We are currently taking preparations for an in vivo therapeutic study of our bicistronic lentiviral construct containing a recombinant HSV-TK and EGFR in a clinically relevant GBM rat model.
Abstract 4691: KRAS mutation specific alkylating pyrrole-imidazole polyamide (KR12) suppresses mutant KRAS expression and inhibits tumor growth by showing accumulation in KRAS mutant xenografts
Authors: Takahiro Inoue, Kiriko Hiraoka, Yusei Suzuki, Hiroyuki Yoda, Takayoshi Watanabe, Atsushi Takatori, Nobuko Koshikawa, Toshinori Ozaki, Hiroki Nagase
Journal: Cancer Research (2015)

Abstract Constitutive active mutations of KRAS are detected in 35-40% of human colon cancers, and almost all of them are the constitutive active missense mutations at codon 12 (80%) or codon 13 (20%). Consistent with these observations, the presence of KRAS mutations has been shown to be associated with malignant properties of tumors as well as a poor clinical outcome of the patients bearing these tumors. Unfortunately, yet no effective anti-cancer drug(s) specifically targeting KRAS mutations have been developed. Hence, we synthesized an alkylating agent conjugated with the Pyrrole-Imidazole polyamide (KR12: PI-polyamide-seco-CBI), which recognized KRAS G12D or G12V mutations at codon12. We have previously found that KR12 has anti-tumor effects in vitro and in vivo. However, it still remains elusive whether KR12 exerts its selective toxicity towards colon cancer cells by penetrating into the tumor tissues and inhibiting the expression of mutant KRAS gene in mouse model of human cancer. To address this issue, we decided to examine the distribution of KR12 using FITC labeled PI polyamide. In vivo imaging of tumor-bearing mice after single intravenous administration demonstrated that the highest fluorescence intensity was seen in the tumor sites 24 hours after injection with showing nuclear localization. Quantitative RT-PCR revealed that KR12 decreased the mutated KRAS expression in tumor tissues obtained from KRAS-heterozygous-mutated-LS180-xenografted mice (G12D heterozygous mutation). Since KR12 showed long lasting accumulation in xenografts we compared the effect of single and multiple administration of KR12. Once a week injection for five to eight weeks resulted in significant suppression of tumor growth in homozygous mutant SW480 (G12V homozygous mutation) xenografts. Surprisingly, both single and multiple treatments of KR12 induced massive tumor volume reduction without affecting body weight gain. These data suggest that KR12 accumulation in colon xenograft tumor tissues may emphasize drug local effect and minimize systemic adverse effect. Citation Format: Takahiro Inoue, Kiriko Hiraoka, Yusei Suzuki, Hiroyuki Yoda, Takayoshi Watanabe, Atsushi Takatori, Nobuko Koshikawa, Toshinori Ozaki, Hiroki Nagase. KRAS mutation specific alkylating pyrrole-imidazole polyamide (KR12) suppresses mutant KRAS expression and inhibits tumor growth by showing accumulation in KRAS mutant xenografts. [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 4691. doi:10.1158/1538-7445.AM2015-4691
Transient Bcl-XL Overexpression in Donor Stem Cells Increases Efficacy of Hematopoietic Stem Cell Transplantation without Increasing the Risk of Leukemogenesis
Authors: Miriam Erlacher, Matthias Kollek, Gesina Voigt, Daniela Bertele, Felix Krombholz, Stefan Schiller, Ana Garcia-Saez, Stephan Geley, Andreas Villunger, Charlotte M Niemeyer
Journal: Blood (2014)
Reduced Intensity Conditioning (RIC) Prior to Allogeneic Stem Cell Transplantation in AML Patients with An Intermediate Risk Karyotype: No Difference in Outcome as Compared to Standard Myeloablative Conditioning (MAC).
Authors: Philipp Hemmati, Gero Massenkeil, Theis Terwey, Stefan Neuburger, Philipp D. le Coutre, Lam G Vuong, Bernd Dörken, Renate Arnold
Journal: Blood (2008)
Analysis of Trends in US Melanoma Incidence and Mortality
Authors: Alex M. Glazer, Richard R. Winkelmann, Aaron S. Farberg, Darrell S. Rigel
Journal: JAMA Dermatology (2016)

The incidence of and mortality from invasive melanoma in the United States has risen steadily for at least the past 2 decades. 1 Similar trends are being seen worldwide despite numerous efforts to enhance primary prevention and early detection, and these increasing rates are having an impact on the public health and economic burden of disease.In 2009, we reported on the status of US melanoma incidence at that time. 2 The purpose of this study was to provide updated information on trends in melanoma incidence and mortality that will help to elucidate the current state of this cancer in the United States.
Prognostic Significance of hOCT1 and ABCG2 Expression in Chronic Myeloid Leukemia Patients Treated with Imatinib
Authors: Yeo-Kyeoung Kim, Hee-Nam Kim, Ri Yu, Il-Kwon Lee, Jae-Sook Ahn, Deok-Hwan Yang, Je-Jung Lee, Hyeoung-Joon Kim
Journal: Blood (2008)