tbuckley/cabot-search huggingface dataset:
Development of a new stool biomarker ELISA for the early detection of colorectal cancer.
Authors: J. Luka, P. M. Arlen, J. A. Bristol
Journal: Journal of Clinical Oncology (2011)

390 Background: An ELISA was developed using NPC-1C, a novel antibody that reacts with an antigen expressed specifically by human colorectal and pancreatic tumor tissues and cell lines. The target antigen that NPC-1C recognizes was shown to be related to MUC5AC, a member of the mucin family of glycoproteins. NPC-1C reacts with neither normal tissues from healthy donors (rare, weak binding to normal colon and esophagus), nor cell lines derived from other tumor types, thereby providing the basis for a proof of concept comparative evaluation with stool from normal healthy donors. Methods: An ELISA that uses NPC-1C antibody as both capture and detection reagent was developed. Samples of stool collected during colonoscopy from colorectal cancer patients (n = 4), stool from people with small polyps (n = 4), stool from people with multiple polyps (n = 2), stool from people with large polyps (n = 3), and stool from healthy adults (n = 13) were applied to the ELISA. A soluble extract of stool was prepared by detergent lysis and centrifugation. The level of NPC-1C-specific MUC5AC antigen measured in this ELISA was compared among all groups. Results: Preliminary results demonstrated that healthy people did not express NPC-1C antigen in their stool. The signal in the assay was similar to background levels (average 723 units). In contrast, people with small polyps had higher levels (average 3,819 units); people with multiple polyps expressed higher levels (average 7,369 units); people with large polyps had even higher levels (average 10,189 units); and colon cancer patients had the highest levels (average 175,983 units), more than 240 times the level of MUC5AC-related antigen compared with healthy people. Conclusions: The proof of concept has been established to correlate the level of NPC-1C reactive antigen, measured by a novel stool-based ELISA, with colon cancer disease progression. The level of NPC-1C-specific MUC5AC detected increased concomitantly with the number and size of polyps observed during colonoscopy, and reached the highest levels in patients with colon cancer. Our goal is to apply this ELISA test for early noninvasive diagnostic screening for colorectal cancer, an area of still largely unmet need. [Table: see text]
Detection of an Unbalanced Ratio Between WT1 Isoforms in Acute Myeloid Leukemia and Its Correlation with Molecular Abnormalities.
Authors: Chiara Calabrese, Gian Matteo Pica, Enrico Bracco, Anna Serra, Francesca Carnuccio, Sonia Carturan, Valentina Campia, Chiara Ghiggi, Fabio Guolo, Angelo Michele Carella, Nicoletta Colombo, Raffaella Grasso, Maurizio Miglino, Francesco Frassoni, Giuseppe Saglio, Daniela Cilloni
Journal: Blood (2012)
Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells
Authors: D T Saenz, W Fiskus, Y Qian, T Manshouri, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, C P Mill, B Sun, P Qiu, T M Kadia, N Pemmaraju, C DiNardo, M-S Kim, A J Nowak, C Coarfa, C M Crews, S Verstovsek, K N Bhalla
Journal: Leukemia (2017)
Abstract 3175: CD38-expressing myeloid-derived suppressor cells promote tumor growth in a murine model of esophageal cancer
Authors: Tatiana A. Karakasheva, Todd J. Waldron, Evgeniy Eruslanov, Ju-Seog Lee, Shaun O'Brien, Devraj Basu, Sunil Singhal, Fabio Malavasi, Anil K. Rustgi
Journal: Cancer Research (2015)

Abstract Myeloid derived suppressor cells (MDSCs) are an immunosuppressive population of immature myeloid cells found in advanced stage cancer patients and mouse tumor models. MDSCs suppress T cell-mediated tumor clearance by production of inducible nitric oxide synthase (iNOS) and arginase, as well as through other mechanisms. The purpose of this study was to identify the factor(s) contributing to the pro-tumorigenic role of MDSCs in esophageal squamous cell carcinoma (ESCC). We have used an unbiased approach to search for changes in global gene expression profile of MDSCs derived from conditional p120-catenin knockout mice (L2-cre;p120ctnf/f, a model of oral-esophageal cancer; Stairs D.B., et al Cancer Cell 2011), compared to immature myeloid cells from age-matched wild-type mice. We have detected a dramatic increase in expression of the Cd38 gene in MDSCs, compared to control cells. CD38 belongs to the ADP-ribosyl cyclase family and possesses both ectoenzyme and receptor functions. It has been described to function in lymphoid and early myeloid cell differentiation, cell activation and neutrophil chemotaxis. We find that CD38 expression in MDSCs is evident in several mouse tumor models, and CD38high MDSCs are more immature than MDSCs lacking CD38 expression, suggesting a potential role for CD38 in the maturation halt found in MDSC populations. CD38high MDSCs also possess a greater capacity to suppress activated T cells, and promote tumor growth to a greater degree than CD38low MDSCs, likely as a result of increased iNOS production. We have identified novel tumor-derived factors, including IL-6, IGFBP-3 and CXCL16, which induce CD38 expression by MDSCs ex vivo. Finally, we have demonstrated that monoclonal antibody-mediated targeting of CD38 results in suppressed tumor growth in vivo in a subcutaneous transplant model of ESCC. In conclusion, we have shown that expression of CD38 plays an important role in MDSC biology by promoting an enhanced immunosuppressive capacity and a more immature phenotype in vivo. We have also detected an expansion of CD38-positive MDSCs in peripheral blood of advanced stage cancer patients and propose targeting CD38 in vivo as an approach to cancer therapy. Supported by NCI P01CA098101. Citation Format: Tatiana A. Karakasheva, Todd J. Waldron, Evgeniy Eruslanov, Ju-Seog Lee, Shaun O'Brien, Devraj Basu, Sunil Singhal, Fabio Malavasi, Anil K. Rustgi. CD38-expressing myeloid-derived suppressor cells promote tumor growth in a murine model of esophageal 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 3175. doi:10.1158/1538-7445.AM2015-3175
Esthetic assessments in implant dentistry: objective and subjective criteria for clinicians and patients
Authors: Jan Cosyn, Daniel S. Thoma, Christoph H. F. Hämmerle, Hugo De Bruyn
Journal: Periodontology 2000 (2016)

Abstract In recent years the scientific community has shown a clear interest in the esthetic outcome of implant treatment. The present paper provides an overview of the esthetic ratings that have been used in implant dentistry. A distinction can be made between objective evaluations by clinicians and subjective evaluations by patients. The former mainly include: midfacial and interproximal soft‐tissue levels; two‐dimensional/three‐dimensional soft‐tissue alterations; assessment of the color match between the natural dentition, on the one hand, and the peri‐implant tissues and the reconstruction, on the other hand; and ordinal indices, such as the pink and white esthetic score. Patient's needs and judgment may differ from objective indicators of implant success and esthetics. As a result, assessing treatment on the basis of patient‐reported outcomes measures should be considered important. Validated questionnaires have been used that mainly assess the impact of oral health on the overall well‐being of individuals. The esthetic judgment of patients is usually based on nonstandardized questions with varying scoring methods, including visual analog scales, Likert and other category scales and open questions. The heterogeneity in scoring systems between studies may compromise proper comparison of objective and subjective esthetic outcomes between studies and therapeutic concepts.
Abstract 2808: Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450
Authors: Ping Chen, Tao Hu, Yane Ma, Xiaoyu Chen, Liping Dai, Ningjing Lei, Ziming Dong, Pei Li
Journal: Cancer Research (2015)

Abstract Esophageal squamous carcinoma (ESCC) may be developed through a progressive sequence from mild to severe dysplasia, carcinoma in situ, and finally, invasive carcinoma. Chemoprevention can block or weaken the influence of development. Recent study has shown luteolin, a bioflavonoid, possesses anti-inflammatory, antioxidant, and anti-proliferative effects, and it might have a preventive effect in this progress. In this study, we focused on the effect of luteolin on cell cycle regulation in human Esophageal Squamous Carcinoma Cell Line EC1 and KYSE450 Cells in vitro and its potential mechanisms. Observations by flow cytometer showed that luteolin inhibited cell cycle progression at G2/M phase in a dose- and time-dependent manner. We also found that luteolin could induce cell apoptosis via decreasing activation of caspase-3 and down-regulation of mitochondrial membrane potential. Western blot results showed the protein expression of cycle related protein CyclinD1 and apoptosis related proteins caspase-3, caspase-9, and Bak were also significantly decreased in luteolin treated cells compared with the non-luteolin treated cells. Our results suggest that the proper use of luteolin might be a practical approach to the prevention of esophageal carcinoma via the inhibition of cell proliferation and other potential high risk regions for this disease. Citation Format: Ping Chen, Tao Hu, Yane Ma, Xiaoyu Chen, Liping Dai, Ningjing Lei, Ziming Dong, Pei Li. Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450. [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 2808. doi:10.1158/1538-7445.AM2015-2808
Preliminary Results of a Phase II Trial of Panobinostat (LBH589) In Refractory Myelodysplastic Syndromes (MDS) Patients
Authors: Ian W. Flinn, Evan Lang, Eric Raefsky, Ralph Boccia, Inés M. Macias-Pérez, Howard A. Burris, John D. Hainsworth
Journal: Blood (2010)
Discontinuation of Lenalidomide in Patients with Transfusion-Dependent Low- and Intermediate-1 Risk Myelodysplastic Syndromes with Del(5q): Sustained Remissions, but Not Cure.
Authors: Aristoteles Giagounidis, Gudrun Göhring, Sabine Haase, Carlo Aul, Brigitte Schlegelberger, Andrea Kuendgen, Regina Herbst, Gerhard Ehninger, Uwe Platzbecker
Journal: Blood (2009)
Abstract 1080: Computational and biochemical discovery of RSK2 as a novel target for epigallocatechin gallate (EGCG)
Authors: Hanyong Chen, Ke Yao, Xiaoyu Chang, Jung-Hyun Shim, Hong-Gyum Kim, Margarita Malakhova, Dong-Joon Kim, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2015)

Abstract The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). Protein interaction with EGCG is a critical step mediating the effects of EGCG on the regulation of various key proteins involved in signal transduction. By using computational docking screening methods for protein identification, we identified a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2), as a novel molecular target of EGCG. RSK2 includes two kinase catalytic domains in the N-terminal (NTD) and the C-terminal (CTD) and its activation requires phosphorylation of both the NTD and CTD. The computer prediction was confirmed by an in vitro kinase assay in which EGCG inhibited RSK2 activity in a dose-dependent manner. Pull-down assay results showed that EGCG could bind with RSK2 at both kinase catalytic domains in vitro and ex vivo. Furthermore, results of an ATP competition assay and a computer-docking model showed that EGCG binds with RSK2 in an ATP-dependent manner. In RSK2+/+ and RSK2-/- murine embryonic fibroblasts, EGCG decreased viability only in the presence of RSK2. EGCG also suppressed epidermal growth factor-induced neoplastic cell transformation by inhibiting histone H3 Ser10 phosphorylation. Overall, these results indicate that EGCG is a novel natural compound for suppressing RSK2 kinase activity. Citation Format: Hanyong Chen, Ke Yao, Xiaoyu Chang, Jung-Hyun Shim, Hong-Gyum Kim, Margarita Malakhova, Dong-Joon Kim, Ann M. Bode, Zigang Dong. Computational and biochemical discovery of RSK2 as a novel target for epigallocatechin gallate (EGCG). [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 1080. doi:10.1158/1538-7445.AM2015-1080
Abstract P6-08-31: Linking genotype to clinical outcome in breast cancer by combining NGS and gene chip data
Authors: Balazs Gyorffy, Lorinc Pongor, Mate Kormos
Journal: Cancer Research (2015)

Abstract Introduction: Next generation sequencing (NGS) provides the possibility to measure mutational status for any part of any gene. However, because of scarce data available to date, linking these mutations to relevant clinical outcome in a large number of patients is not possible. Aim: Our goal was to combine available genotype data generated by using NGS with gene expression data generated by gene chips to establish a framework to assess the effect of genotype on clinical outcome. Methods: NGS data generated by the TCGA consortia and publicly available gene chip data obtained from the GEO and EGA repositories were utilized. NGS data was processed using MuTect, SNPeff, GRCh37 and R. RNA-seq data was normalized using DEseq. Gene chip data was MAS5 normalized. Generation of the transcriptomic fingerprint for mutation status was computed by ROC utilizing the RNA-seq data. In the gene chip data, the average expression of significant genes identified was designated as a metagene for the given genotype. Correlation to survival for this metagene was assessed by computing Cox regression and plotting Kaplan-Meier survival plots. Finally, we have set up an online interface to enable running the analysis for any selected gene. Results: The database contains 332 NGS samples containing mutational status for 22,938 genes and RNA-seq data for 10,987 genes. The gene chip database contains 5,934 patients with 10,987 genes plus detailed clinical characteristics and survival data. We evaluated correlation to outcome for previously identified genes harboring the ten most common somatic mutations in breast cancer. Of these, TP53 (n of mutations out of 332=93, hazard rate=0.51, p&amp;lt;1E-16), AKT1 (n=18, HR=1.6, p=1.6E-15), PIK3CA (n=119, HR=1.5, p=8.5E-12), MAP3K1 (n=20, HR=1.4, p=1.3E-08), CDH1 (n=34, HR=1.3, p=4.4E-07), and RB1 (n=21, HR=1.3, p=7E-06) reached statistical significance while PI3K, PTEN, CDKN1B and GATA3 were not significant or had insufficient number of mutated samples. Discussion: By connecting genotype to gene expression signature and employing this signature for survival analysis we have set up a pipeline enabling the functional validation of a discovered mutation for any gene in a large breast cancer cohort. Citation Format: Balazs Gyorffy, Lorinc Pongor, Mate Kormos. Linking genotype to clinical outcome in breast cancer by combining NGS and gene chip data [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-31.
Current Clinico-Epidemiological Characteristics of Adult T-Cell Leukemia-Lymphoma (ATL) Based on the 11th Nationwide Survey in Japan
Authors: Kisato Nosaka, Masako Iwanaga, Kenichi Ishizawa, Yoji Ishida, Kaoru Uchimaru, Kenji Ishitsuka, Masahiro Amano, Takashi Ishida, Yoshitaka Imaizumi, Naokuni Uike, Atae Utsunomiya, Koichi Ohshima, Kazuhiro Kawai, Junji Tanaka, Yoshiki Tokura, Kensei Tobinai, Toshiki Watanabe, Kunihiro Tsukasaki
Journal: Blood (2015)
Exploring the Immune Microenvironment of Diffuse Large B Cell Lymphoma in a Tissue Microarray: Predicting Survival with a Score That Incorporates Macrophages, Cytotoxic and Regulatory T Cells
Authors: Rita Coutinho, Andrew James Clear, David Andrew Owen, Paul Greaves, Simon L. Hallam, Andrew Wilson, Janet Matthews, Maria Calaminici, John G. Gribben
Journal: Blood (2011)
Clinical Follow-up of Patients with Myeloproliferative Neoplasms Presenting Skin Ulcers During Treatment with Hydroxyurea
Authors: Roberto Latagliata, Michele Cedrone, Nicoletta Villivà, Cinzia De Gregoris, Massimo Breccia, Antonio Spadea, Marianna De Muro, Agostino Tafuri, Barbara Anaclerico, Stefano Felici, Mariella D'Andrea, Enrico Montefusco, Elisabetta Abruzzese, Francesca Spirito, Sabrina Leonetti Crescenzi, Umberto Recine, Maria Gabriella Mazzucconi, Luciana Annino, Giuseppe Cimino, Giuseppe Avvisati, Maria Concetta Petti, Giuliana Alimena, Marco Montanaro, Alessandro Andriani
Journal: Blood (2011)
Corrigendum to “Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs” [Biomaterials 76C (2015) 399–407]
Authors: Li Fan, Yongsheng Zhang, Fuli Wang, Qian Yang, Jiali Tan, Renata Grifantini, Hong Wu, Chaojun Song, Boquan Jin
Journal: Biomaterials (2016)
Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response (CR) plus complete marrow response (mCR) of greater than 50% in refractory relapse (R-R) acute lymphocytic leukemia (ALL).
Authors: E. Jabbour, S. M. O'Brien, D. A. Thomas, F. Ravandi, S. York, M. Kwari, S. Faderl, T. M. Kadia, C. Wilson, R. Tarnai, A. S. Advani, G. Garcia-Manero, J. E. Cortes, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6507 Background: Patients (pts) with R-R ALL have a poor prognosis. CD22 is highly expressed in ALL. IO is active in CD22-positive lymphomas. Methods: Pts with R-R ALL received IO 1.8 mg /m2 IV over 1hr every 3 weeks. First 3 pts received 1.3 mg / m2 in course 1. Children were eligible for study after 10 adults were treated; first 3 children received 1.3 mg/m2. Study started June 2010. Results: 40 pts were treated; 36 are evaluable after 1 course. Median age 35 yrs (range 6-80); 7 pts ≥ 60 yrs; Ph+ in 3, t(4:11) in 5, other abnormalities in 18. CD22 expressed in > 50% blasts in all pts, > 90% in 20. Median number courses so far 2 (1-5). 9 pts received IO as salvage 1 (S1) 21 as, salvage 2 (S2), 10 as ≥ salvage 3 (S3). 6 pts had allo SCT before IO. Overall, 9/36 pts (25%) achieved CR, 11 had mCR (31%), 16 were resistant, 1 died within 4 wks. Overall, CR+mCR (OR) was 56%: S1 6/9 (66%); S2 10/21 (48%); S3 4/10 (40%). No clear correlations between OR and pts / ALL characteristics or with CD22 expression ≥ vs. < 90%. In 12 pts with evaluable pharmacokinetics studies: 3-hr I0 level > 100 ng/ml associated with OR in 5/5 vs. 0/7 if I0 level < 100 ng/ml. In responders, 70% are alive at 6 mos; in non-responders, median survival 2.5 mos. Fever and mild hypotension occurred in most pts on days 1-2 and resolved with support. Liver function abnormalities (LFA) were noted as IO related in 9 (25%), severe in 4 (11%). 2 pts had liver biopsies showing periportal fibrosis (after 1 and 5 courses). 12 pts were able to proceed to allo SCT; 3 pts post-allo SCT developed venoocclusive disease, 2 receiving second allo SCT. Conclusions: IO is likely the single most active single agent tested so far in R-R ALL. LFAs occur and are reversible. IO activity in ALL, alternative schedules (weekly IO), and IO combinations should be pursued.
Interim Restaging FDG-PET/CT to Guide Use of High Dose Sequential Induction Therapy with Rituximab-Dose-Intensive Cyclophosphamide, Etoposide, Cisplatin (RDICEP) and Rituximab-Carmustine, Etoposide, Cytarabine, Melphalan (RBEAM) and Autologous Stem Cell Transplantation (ASCT) for Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL). ClinicalTrials. Gov Identifier: NCT00530179.
Authors: Douglas A. Stewart, Peter Duggan, Nizar J Bahlis, Andrew Daly, Michelle Geddes, Reinhard Kloiber, Christian Fibich, David Blair Macdonald, Isabelle Bence-Bruckler
Journal: Blood (2009)
Conjunctival Biopsy to Guide Treatment of Chronic Ocular Gvhd
Authors: Pritesh R. Patel, Sonal Ghandi, Snehal Sonawane, Sapna Tibrewal, Saumad Jassim, Sujata Gaitonde, Santosh L Saraf, Sandeep Jain, Damiano Rondelli
Journal: Blood (2012)
Phase I/II trial of vandetanib and bortezomib in adults with locally advanced or metastatic medullary thyroid cancer: Phase I results.
Authors: A. W. Gramza, S. A. Wells, S. Balasubramaniam, A. T. Fojo
Journal: Journal of Clinical Oncology (2011)

5565 Background: Vandetanib (V), a multi-targeted kinase inhibitor, is effective in the treatment of metastatic medullary thyroid cancer (MTC). Bortezomib (B), a proteosome inhibitor, is approved for the treatment of multiple myeloma. Preclinical evidence shows that the addition of B enhances V's activity against MTC cell lines. The phase I portion of a phase I/II study designed to assess the safety, tolerance, and activity of V + B in patients with MTC has completed accrual. Methods: Patients with advanced solid tumors, ECOG 0-1, and adequate organ function were treated on a dose escalation schema with B (1-1.3 mg/m2) IV days 1, 4, 8, and 11 and V (100 – 300 mg) orally daily (28-day cycles). B/V were continued until unacceptable toxicity or progressive disease, with optional continuation of V alone if toxicity was B-related. Results: 21 patients were enrolled (3-09 to 11-10) and assigned B/V at 1/100 (3), 1.3/100 (6), 1.3/200 (6), 1.3/300 (6). Patients received a median of 4 cycles of B/V (range: 1-10), with 13 escalating to 1.3/200 and 10 to 1.3/300. Presently, 1 remains on B/V and 10 on V alone. G3 toxicities were: hypertension (24%), fatigue (19%), thrombocytopenia (10%), diarrhea (10%), arthralgia (10%), with keratocanthoma, hyperkalemia, pulmonary hemorrhage, edema, and prolonged QT each in 1 (5%). There were no drug-related G4/5 toxicities. There was 1 DLT, G3 thrombocytopenia, at B/V 1.3/200 in cycle 2. The toxicity resolved and the patient received cycle 3 and subsequent cycles at 1/100. No further DLTs were seen. Of the 17 patients with MTC: 16 had primary resection, 7 had prior radiation, and 7 had prior systemic therapy. All had metastatic disease. Median calcitonin and CEA levels were 5289 and 113, respectively. 5 (29%) had partial responses (PR) and 8 (47%) had stable disease (SD). 6 SD have lasted for > 6 months and may achieve PR. A correlation was not found between RECIST response and calcitonin or CEA levels. Pharmacokinetic data are pending. Conclusions: The MTD of B/V is B 1.3 mg/m2 IV days 1,4,8, and 11 and V 300mg orally daily. This regimen is effective, safe, and well tolerated. We are currently enrolling MTC patients to the phase II portion of this trial to compare the MTD of B/V versus V 300 mg.
Therapy-Related Myelodysplasia/Acute Myeloid Leukemia (t-MDS/AML) After Conventionally-Treated Breast Cancer: Impact of Cytogenetics on Outcome After Allogeneic Hematopoietic Cell Transplantation (HCT),
Authors: Rajinder S. Grover, Vinod Pullarkat, Can-Lan Sun, Smita Bhatia, Stephen J. Forman
Journal: Blood (2011)
Neonatal Megakaryocytes Do Not Mature Normally In the Absence of Thrombopoietin In Vivo: Potential Role of Developmental Differences In CXCR4 Expression
Authors: Francisca Ferrer-Marin, Ravi K. Gutti, Zhi-Jian Liu, Joseph Italiano, Zhongbo Hu, William Slayton, Martha Sola-Visner
Journal: Blood (2010)