tbuckley/cabot-search huggingface dataset:
Serum auto-antibody testing for the screening of non-small cell lung cancer: techniques to improve accuracy
Authors: L. Zhong, J. Lou, Y. Yen, K. H. Kernstine
Journal: Journal of Clinical Oncology (2008)

22216 Background: Early detection is crucial to reducing cancer mortality. Currently, there is no single test available to identify early stage non-small cell lung cancer (NSCLC). Previously, we reported a panel of auto-antibodies used to detect early-stage and occult NSCLC prior to discovery on computed tomogram. From serum samples of NSCLC patients drawn 0 to 5 years before radiographic detection, we achieved 91.3% sensitivity and 91.3% specificity to detect stage I NSCLC and 82.6% of sensitivity and 87.5% specificity to discover occult NSCLC. In this study, we repeated the biopanning process to further confirm and potentially increase the sensitivity and specificity of the test. Methods: Using 5-pooled NSCLC sera from one NSCLC T7 cDNA in-frame phage library and after 4 cycles of biopanning enrichment, 2000 phage clones were randomly picked and spotted onto nitrocellulose coated slides along with 400 empty phage clones and healthy human serum as negative and positive controls, respectively. Results: After comparative screening with 28 stage I NSCLC patient sera and 28 healthy control serum samples, 54 clones were found to have significant difference (P<0.05), while screening with 20 stage II-IV NSCLC patient serum and 20 healthy control serum samples, 162 clones were found to have significant difference (P<0.05). Among these selected clones, 15 clones were found to be common between the two groups. A panel consisting of as few as 22 clones appeared to achieve 100% sensitivity and 100% specificity using discriminant analysis differentiating 48 patients and 48 matched controls. We sequenced the top 20 of the most predictive clones and found 9 of them are well characterized tumor-associated proteins. Conclusions: Currently, this panel of markers is under evaluation and validation with additional samples to assess the predictive accuracy. Improved accuracy should allow earlier intervention and superior results in the treatment of NSCLC. No significant financial relationships to disclose.
204. HER2-Specific Chimeric Antigen Receptor T Cells for the Treatment of Breast-to-Brain Metastasis
Authors: John P. Murad, Dileshni Tilakawardane, Brenda Aguilar, Anthony Park, Ethan Gerdts, Aniee Sarkissian, Alfonso Brito, Josh Neman, Renate Starr, Brenda Chang, Wen-Chung Chang, Sarah Wright, Behnam Badie, Stephen J. Forman, Christine E. Brown, Saul J. Priceman
Journal: Molecular Therapy (2016)

Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells has demonstrated robust and durable clinical efficacy in patients with CD19+ B-cell malignancies. Broader application of this approach to brain and other advanced solid tumors is an immediate goal for the field and is presently under intense investigation. In 2014, 40,000 individuals in the U. S. alone succumbed to breast cancer, primarily as a result of metastatic disease. Approximately 30 percent of breast cancer patients carry an amplification of the HER2 gene and/or HER2 over-expression, which confers a particularly poor prognosis. Among the most common sites of HER2-positive breast cancer metastases is the brain. For patients with breast cancer that has metastasized to the brain, the 1-year survival rate is a dismal 20 percent. Despite clinical successes in both preventing relapse and treating systemic disease with HER2-targeted therapies, the currently available agents are only modestly effective in managing brain metastasis. Our group has demonstrated safety and transient anti-tumor responses in two U. S. FDA-authorized phase I clinical trials evaluating local intracranial adoptive transfer of CAR T cells in glioma patients. Our current project builds on this clinical experience with locally administered CAR T cells that specifically target HER2 for the treatment of breast-to-brain metastasis. Our lab has initiated design and testing of CAR T cell therapy targeting HER2 based on an scFv derived from trastuzumab. We anticipate that local intracranial delivery will enhance therapeutic response, while reducing the likelihood of off-tumor systemic toxicities as previously observed. Importantly, HER2 expression in normal brain tissue is limited, supporting HER2 as a therapeutic target in brain metastasis. Our innovative CAR T cell platform focuses on engineering central memory T cells (Tcm) for therapeutic application, with the intent of improving persistence of T cells after infusion, a critical parameter correlated with ultimate therapeutic success. Herein, we have evaluated several HER2-CAR constructs incorporating either the CD28 or 4-1BB co-stimulatory domain using both in vitro T cell functional assays as well as orthotopic patient-derived xenograft models of breast-to-brain metastasis. While HER2-28ζ and HER2-BBζ CAR T cells similarly kill HER2+ breast cancer cells in vitro, BBζ CARs demonstrate lower induction of the exhaustion marker PD-1 and proliferate better compare with 28ζ CARs. Both HER2-CARs similarly lead to tumor eradication and prolonged survival. Based on these data, we have successfully developed HER2-specific CAR T cells, and plan to clinically develop these CARs for the treatment of HER2+ metastatic disease.
Investigation of Urine/Plasma Biomarkers to Predict Tolerance and Graft-Versus-Host Disease Post Allogeneic Stem Cell Transplantation.
Authors: Christin Human, Sylvia Borchers, Michael Stadler, Helmut Diedrich, Jürgen Krauter, Christine Falk, Arnold Ganser, Eva M Mischak-Weissinger
Journal: Blood (2012)
Abstract 3078: Epigenetic regulation of miR-138 confers cancer stem cell characteristics of renal cell carcinoma
Authors: Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Elizabeth Hernandez, John Santoyo, Jer-Tsong Hsieh
Journal: Cancer Research (2015)

Abstract Chemotherapy is the standard care for metastatic disease, in renal cell carcinoma (RCC), the outcome of chemotherapy only prolongs short survival of patients. The reason for the resistance of RCC to chemotherapy is not fully understood, although it has been speculated that overabundance of ATP-binding cassette (ABC)/p-glycoprotein transporter system in RCC might be the reason to repel various chemotherapeutic agents away from the cancer cell. Meanwhile, cancer stem cells (CSC) theory has also focused a significant attention in recent years as a potential explanation for drug resistance and metastasis of RCC. In this study, we demonstrate that drug resistant RCC cells exhibit CSC phenotypes and miR-138 that is significantly downregulated in RCC acted critical role in suppressing CSC phenotype by targeting ABC transporter ABCA13 and oncogenic histone methyltransferase EZH2. Importantly, miR-138 levels were significantly enhanced by treatment of DNA hypomethylating agent (i.e., 5-aza) or histone deactylases inhibitor (i.e., TSA). Epigenetic silencing of tumor-suppressive micro-RNAs has been shown a key oncogenic mechanism for the activation of oncogenes in tumors. Indeed, depletion of miR-138 promoted CSC phenotype followed by enhanced expressions of ABCA13 and EZH2. Furthermore, a novel tumor suppressor DAB2IP can inhibit DNA methyltransferase 1 (DNMT1) activity, which results in miR-138 expression. Taken together, this study identifies the new role of miR-138 in RCC-CSC and unveils a unique regulation of tumor suppressor protein in DNMT1. Overall study provides not only a new biomarker of RCC-CSC and but also potential therapeutic strategy of targeting drug resistant RCC. Citation Format: Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Elizabeth Hernandez, John Santoyo, Jer-Tsong Hsieh. Epigenetic regulation of miR-138 confers cancer stem cell characteristics of renal cell carcinoma. [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 3078. doi:10.1158/1538-7445.AM2015-3078
Phase 2 Study of MLN8237, An Investigational Aurora A Kinase (AAK) Inhibitor In Patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndromes (MDS)
Authors: Stuart L Goldberg, Pierre Fenaux, Michael D Craig, Emmanuel Gyan, John Lister, Jeannine Kassis, Arnaud Pigneux, Gary J Schiller, JungAh Jung, E. Jane Leonard, Howard Fingert, Peter Westervelt
Journal: Blood (2010)
Abstract 3008: CEP55 is a determinant of genomic instability in aneuploid breast cancer cells and facilitates anti-mitotic drugs resistance by interacting directly with HSF1
Authors: Murugan Kalimutho, Nicola Waddell, Jessie Jeffry, Sriganesh Srihari, Kum Kum Khanna
Journal: Cancer Research (2015)

Abstract Centrosomal proteins have long been known to act as a scaffolds, spindle checkpoint regulators as well as key regulating elements of microtubule organizing centre, hence as an essential component of cell cycle progression. CEP55 is a centrosomal protein originally identified as an indispensable regulator of cytokinesis, the final stage of cell division that divides cytoplasm equally amongst two daughter cells. Failure to faithfully complete cytokinesis due to loss of CEP55 resulted in primary genetic lesion leading to multinucleated cells, thus promotes tumourigenesis and aneuploidy. CEP55 has been to shown elevated in wide range of cancers including breast cancer, however the molecular mechanisms on how CEP55 mediated genomic instability in cancers are still not well understood. To decipher the functional role of CEP55 in regulating genomic instability in breast cancer, through a series of in-vitro and in-vivo experiments we found that high levels of CEP55 is significantly associates with basal-like breast cancer subtype with poor overall survival, relapse free survival and distant-metastasis free survival. Furthermore, we found that depletion of CEP55 decreased cell viability due to induction of apoptosis and hamper primary tumour growth due to clearance of aneuploid cells that are particularly important in oncogenic transformation. In addition, depletion of CEP55 hindered premature exit of mitotic arrested cells and this is partly mediated through CEP55-dependent interaction with HSF1 during mitosis to facilitate development of aneuploidy. Strikingly, we found that CEP55 mediates anti-mitotic drug resistance to docetaxel and PLK1 inhibition. Depletion of CEP55 increased sensitivity to anti-mitotic drugs in particular docetaxel or PLK1 inhibitor, providing a rationale to target CEP55 and its dependent-pathways in aggressive and aneuploid breast cancer. Citation Format: Murugan Kalimutho, Nicola Waddell, Jessie Jeffry, Sriganesh Srihari, Kum Kum Khanna. CEP55 is a determinant of genomic instability in aneuploid breast cancer cells and facilitates anti-mitotic drugs resistance by interacting directly with HSF1. [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 3008. doi:10.1158/1538-7445.AM2015-3008
Pathologic Evaluation of Skin Tumors With Ex Vivo Dermoscopy With Derm Dotting
Authors: Marc Haspeslagh, Isabelle Hoorens, Nele Degryse, Ine De Wispelaere, Annemarie Degroote, Sarah Van Belle, Jan Verboven, Katrien Vossaert, Fabio Facchetti, Jo Van Dorpe, Sofie De Schepper, Lieve Brochez
Journal: JAMA Dermatology (2016)

Ex vivo dermoscopy (EVD) with derm dotting (DD) improves clinicopathologic correlation and the quality of diagnosis in skin tumors.To compare the diagnostic performance of the standard method of skin biopsy processing with the practice of EVD with DD.This retrospective study compares the diagnostic performance in 6526 skin biopsy specimens examined from 2008 to 2010 with a standard method of processing with 8584 biopsy specimens examined in 2015 with EVD and DD. Data were analyzed from January 1 to March 31, 2016. A total of 15 110 skin biopsy specimens were included. The biopsy specimens from 2008 to 2010 were processed in a hospital-based general pathology laboratory; the biopsy specimens from 2015 were processed in a private dermatopathology laboratory. Biopsy specimens from both periods were diagnosed by the same dermatopathologist.The primary outcome measures were clinicopathological characteristics, usefulness of EVD with DD, and turnaround times (TATs).Use of EVD with DD increased the detection of positive section margins in nonmelanoma skin cancer from 8.4% to 12.8%. The most significant increase was seen in Bowen disease, invasive squamous cell carcinoma, and a superficial type of basal cell carcinoma (BCC). With EVD and DD, a specific clinicopathologic diagnosis was made in 27.7% of nevi compared with only 10.3% using the standard method. The incidence of moderately and severely dysplastic nevi increased from 1.0% to 7.2% and from 0.6% to 1.4%, respectively. The detection of ulceration in melanomas with thicker than 1 mm increased from 24.0% to 31.3%. The number of nevi-associated melanomas increased from 15.5% to 33.3%. The number of collision lesions from 0.07% to 1.07%. The TAT for nevi decreased from 2 days to 1 day, for melanomas from 5 days to 2 days, and for BCC from 2 days to 1 day.Ex vivo dermoscopy and DD with adapted sectioning in a dermatopathology setting allows a more accurate and less time consuming histopathologic diagnosis of skin tumors. These findings suggest that pathologists involved in skin tumor evaluation should be encouraged to learn dermoscopy and replace random transverse cutting with lesion-specific and DD-guided cutting.
Abstract B19: Kras mutation imparts neoplastic potential on duct cells but not acinar cells in a mouse model of obstructive chronic pancreatitis
Authors: Fong C. Pan, Jessica N. Kim, Chanjuan Shi, Mary K. Washington, Maike Sander, Maureen Gannon, Robert D. Beauchamp, Christopher V. Wright, Anna L. Means
Journal: Cancer Research (2016)

Abstract Understanding the progression of human pancreatic cancer is difficult due to the late stage of diagnosis of this deadly disease. We must therefore rely upon robust model systems to understand how pancreatic cancer arises, how its acute and chronic phases of progression are regulated, and how best to identify and treat it, hopefully still in the early stage. Models of pancreatic ductal adenocarcinoma (PDAC) that accurately reflect human disease are still being developed. To mimic human disease, PDAC must arise from mutations occurring in adult animals and with etiologies relevant to humans. We developed a new mouse model that incorporates obstructive chronic pancreatitis with tissue-specific, adult-onset expression of mutant Kras. We found that KrasG12D expression in duct cells but not in acinar cells led to progression of metaplastic ducts to eventual dysplasia and cancer. In early-stage disease, Kras mutation in acinar cells led to increased acinar-to-ductal metaplasia but did not downregulate p53, thus leading to reduced cell survival. Ducts naturally express much lower p53 levels, however, and there was increased survival of KrasG12D-mediated, duct-derived metaplastic cells. Furthermore, acinar cells upregulated Pdx1 during acinar-to-ductal metaplasia while duct cells did not do so during their metaplastic transition. Without chronic pancreatitis, Kras mutation in acinar cells causes abundant Pancreatic Intraepithelial Neoplasm (PanIN)-like lesions. However, overexpression of Pdx1 in acinar cells in this context permitted acinar-to-ductal metaplasia but prevented PanIN-like lesion formation, suggesting that Pdx1 can repress neoplastic progression. In summary, in the setting of obstructive chronic pancreatitis, ducts are the principal source of cancer development via reduced Pdx1 and p53 levels and increased cell survival. Citation Format: Fong C. Pan, Jessica N. Kim, Chanjuan Shi, Mary K. Washington, Maike Sander, Maureen Gannon, Robert D. Beauchamp, Christopher V. Wright, Anna L. Means.{Authors}. Kras mutation imparts neoplastic potential on duct cells but not acinar cells in a mouse model of obstructive chronic pancreatitis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B19.
618. Directional Transduction of AAV-5 Vectors in the NHP Brain
Authors: Bas Blits, Lluis Samaranch, John Bringas, Waldy San Sebastian, Krystoff Bankiewicz, Harald Petry
Journal: Molecular Therapy (2016)

This study was performed to investigate the delivery of AAV vectors into the putamen and thalamus of nonhuman primates. The vectors were delivered to the targeted brain regions by MRI-guided convection enhanced delivery. Special attention was given to the analysis of axonal transport and levels of transduction. Recombinant AAV is an excellent candidate for delivery of therapeutic molecules to the central nervous system to target neurodegenerative diseases. UniQure has succeeded in developing a proprietary platform manufacturing technology that allows safe, effective, cGMP-compliant, economically feasible and commercially scalable manufacturing of AAV. UniQure's novel approach is based on the use of a combination of recombinant baculoviruses and insect cells. Using our production platform, two AAV stocks encoding GDNF or GFP were generated. At eight weeks following infusion into the thalamus, for instance, massive transduction of the thalamus, cortex, striatum and substantia nigra was observed indicating both anterograde and retrograde transduction. At the site of injection, transduction was both glial and neuronal, whereas off site transduction was mainly neuronal. Following injection of a lower AAV volume into the putamen, transduction was limited to areas within the putamen and substantia nigra suggesting only anterograde transport of viral particles. These data indicate a dose dependent anterograde or retrograde transport mechanism. This data set confirms that production of AAV using the (scalable) baculovirus-based platform results in an effective vector that is able to mediate expression patterns that can be used to develop an AAV-mediated therapeutic strategy to treat neurodegenerative diseases.
Spending on Children’s Health Care in the United States
Authors: Rachel L. Garfield
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Phase 2 Study of Carfilzomib (CFZ) with or without Filanesib (FIL) in Patients with Advanced Multiple Myeloma (MM)
Authors: Jeffrey A Zonder, Saad Usmani, Emma C. Scott, Craig C. Hofmeister, Nikoletta Lendvai, Jesus G. Berdeja, Larry D. Anderson, Parameswaran Hari, Seema Singhal, Gregory Orloff, Michael Craig, Jason Valent, Wes Lee, Lowell Hart, J Hrom, Stephano Tarantolo, Edward Faber, Gary J Schiller, Jennifer Schreiber, Colleen Oliver, Selena A Rush, Brian Tunquist, Mieke Ptaszynski, Noopur S. Raje
Journal: Blood (2015)
Glycogen Synthase Kinase-3 (GSK3) Inhibition with Lithium in Combination with Tretinoin Induces Differentiation in Non-Promyelocytic Acute Myeloid Leukemia (AML)
Authors: Masumi Ueda, Paolo F. Caimi, Tammy Stefan, Hillard M. Lazarus, Brenda Cooper, Marcos de Lima, Stanton L. Gerson, David N. Wald
Journal: Blood (2015)
Human lymphoid organ dendritic cell identity is predominantly dictated by ontogeny, not tissue microenvironment
Authors: Gordon F. Heidkamp, Jil Sander, Christian H. K. Lehmann, Lukas Heger, Nathalie Eissing, Anna Baranska, Jennifer J. Lühr, Alana Hoffmann, Katharina C. Reimer, Anja Lux, Stephan Söder, Arndt Hartmann, Johannes Zenk, Thomas Ulas, Naomi McGovern, Christoph Alexiou, Bernd Spriewald, Andreas Mackensen, Gerold Schuler, Burkhard Schauf, Anja Forster, Roland Repp, Peter A. Fasching, Ariawan Purbojo, Robert Cesnjevar, Evelyn Ullrich, Florent Ginhoux, Andreas Schlitzer, Falk Nimmerjahn, Joachim L. Schultze, Diana Dudziak
Journal: Science Immunology (2016)

In mice, conventional and plasmacytoid dendritic cells (DCs) derive from separate hematopoietic precursors before they migrate to peripheral tissues. Moreover, two classes of conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) have been shown to be transcriptionally and functionally distinct entities. In humans, these three DC subtypes can be identified using the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a large number of human individuals, we demonstrate that DC subpopulations in organs of the lymphohematopoietic system (spleen, thymus, and blood) are strongly defined by ontogeny rather than by signals from the microenvironment. In contrast, DC subsets derived from human lung or skin differed substantially, strongly arguing that DCs react toward modulatory signals from tissue microenvironments. Collectively, the data obtained in this study may serve as a major resource to guide further studies into human DC biology during homeostasis and inflammation.
Leveraging an NQO1 Bioactivatable Drug for Tumor-Selective Use of Poly(ADP-ribose) Polymerase Inhibitors
Authors: Xiumei Huang, Edward A. Motea, Zachary R. Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A. Kilgore, Molly A. Silvers, Praveen L. Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G. Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S. Williams, John D. Minna, Muhammad Beg, David E. Gerber, Erik A. Bey, David A. Boothman
Journal: Cancer Cell (2016)