tbuckley/cabot-search huggingface dataset:
Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer
Authors: Kristen M. Hege, Emily K. Bergsland, George A. Fisher, John J. Nemunaitis, Robert S. Warren, James G. McArthur, Andy A. Lin, Jeffrey Schlom, Carl H. June, Stephen A. Sherwin
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. <h3>Methods</h3> Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 10<sup>10</sup> total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72. <h3>Results</h3> Fourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14&nbsp;weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48&nbsp;weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had <sup>111</sup>Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed. <h3>Conclusion</h3> These findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity.
Decoding the RNA Editome of Normal Versus Malignant Progenitor Cell Aging Short Title: RNA Editing in Normal Aging and MDS/AML Stem Cells
Authors: Leslie A Crews, Qingfei Jiang, Larisa Balaian, Heather Leu, Nathan Delos Santos, Angela C Court, Anil Sadarangani, Sheldon Morris, Rainer F. Storb, Anna Kulidjian, Edward D. Ball, Catriona Jamieson
Journal: Blood (2016)
Image-guided near-infrared fluorescent sentinel lymph node mapping in human breast cancer
Authors: S. Troyan, S. Gibbs-Strauss, S. Gioux, R. Oketokoun, F. Azar, A. Khamene, V. Kianzad, M. Rosenberg, B. L. Clough, J. V. Frangioni
Journal: Journal of Clinical Oncology (2009)

e11591 Background: Breast cancer surgery is presently performed without real-time image-guidance. We have developed a novel optical imaging system for image-guided surgery that uses invisible near-infrared (NIR) fluorescent light to highlight structures on the surgical field with high sensitivity, specificity, and contrast. We have also performed the first human clinical trial of the imaging system in women undergoing SLN mapping for breast cancer. Methods: We used a portable imaging system with an articulating arm that has 6 degrees of freedom, high power LED light source, custom optics, custom software, and sterile drape. The imaging system provided simultaneous and real-time imaging of color video and NIR fluorescence at up to 15 frames per second. N = 6 women with biopsy- confirmed breast cancer undergoing SLN mapping gave informed consent. All subjects received conventional mapping with Tc-99m sulfur colloid using a handheld gamma probe as well as NIR fluorescence-guided SLN mapping using a mixture of indocyanine green (ICG) diluted to a final concentration of 10 μM in human serum albumin (ICG:HSA). Results: The imaging system was easy to position in the operating room, with the articulating arm providing 50” horizontal reach and 70” vertical reach. Working distance to the patient was 18”. NIR fluorescence excitation was 20 mW/cm2 at 760 nm. NIR-depleted white light was 40,000 lux. A total of 1.6 ml of ICG:HSA was injected intra-tumorally and peri-tumorally and the site massaged for 5 min. 8 of 9 SLNs identified by Tc- 99m sulfur colloid were also identified by NIR fluorescence. However, NIR fluorescence identified an SLN, confirmed to have cancer in it, that was not identified by Tc-99m sulfur colloid. These differences were consistent with asynchrony in the injection techniques. Unlike the gamma-ray probe, NIR fluorescence provided high-resolution, large area optical imaging of the surgical field, and helped guide surgical resection. Conclusions: In this 6-patient pilot study, a novel NIR fluorescence optical imaging system was used for the first time, and provided real-time image-guided surgery for SLN mapping of breast cancer. No significant financial relationships to disclose.
Discrepancy between treatment goals documentation by oncologists and their understanding among cancer patients.
Authors: Varun Monga, Hassan Kaleem, Sarah C Mott, Anna M Button, Gideon Zamba, Mohammed M. Milhem
Journal: Journal of Clinical Oncology (2015)

e20574 Background: Discussion of treatment goals between oncologists and patients can be challenging. Treatment goal discussions are frequently not incorporated in patient charts. Patients frequently misunderstand goals of cancer therapy. BEACON is a health link software program used to create and implement standardized order sets for various chemotherapy protocols, which includes treatment goal field. Discrepancy between treatment goals documentation by oncologists and their understanding by patients at an academic medical center has not been studied. Methods: Patients above age of 18 with established diagnosis of cancer irrespective of the stage receiving their first cycle of chemotherapy were interviewed. Patients’ recall of discussions with their oncologist regarding therapy intent was assessed. Patient’s answers were compared to the documentation found either in the treatment goal field in BEACON, clinic note or standardized consent forms. McNemar’s test was utilized given the paired nature of the design. A rate of 33% discordance was posited as a threshold which is too high in the clinical sense. A one-sample proportion test was used to evaluate whether the overall observed rate of discordance was significantly different from the proposed 33% rate. All tests were two-sided and tested at the 5% significance level. Results: 207 eligible patients were interviewed. 5% were clinical trial participants. BEACON was utilized 57 % of times to document treatment goals. Oncologist identified treatment goals were not documented in either patient charts or BEACON in 24.6% cases and had to be excluded. There was no significant difference in the directionality of discordance. Inter-rater agreement between patient and oncologist was found to be adequate (κ = 0.64). The overall rate of discordance (17.29%) was found to be significantly less than the proposed acceptable level of 33% (p < 0.01). Conclusions: Electronic entry of treatment goals as a part of chemotherapy order set increases its use and results in higher rate of documentation. Discordance between documentation of goals of therapy and their understanding exists indicating lack of proper communication between oncologists and their patients.
Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation
Authors: Xinghui Li, Zhibin Zhang, Lupeng Li, Wei Gong, Audrey J. Lazenby, Benjamin J. Swanson, Laura E. Herring, John M. Asara, Jeffrey D. Singer, Haitao Wen
Journal: The Journal of Experimental Medicine (2017)

Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation. The inhibitory effect of CUL3 on OGT expression is dependent on nuclear factor E2–related factor-2 (Nrf2), which binds to the Ogt promoter region and increases gene transcription. Myeloid deletion of Cul3 led to defective STAT3 phosphorylation in colon macrophages, which was accompanied by exacerbated colonic inflammation and inflammation-driven tumorigenesis. Thus, this study identifies a new form of posttranslational modification of STAT3, modulating its phosphorylation, and suggests the importance of immunometabolism on colonic inflammation and tumorigenesis.
Fludarabine and Busulfan-Based Reduced Intensity Conditioning (RIC) Allogeneic HLA-Identical Transplantation (allo-SCT) with or without Anti-Thymocyte Globulin (ATG): Comparison between Two Prospective Studies in Patients with Myeloid Malignancies.
Authors: Mohamad Mohty, R. Martino, C. Faucher, J.A. Perez-Simon, N. Vey, M.D. Caballero, J.A. Gastaut, J. San Miguel, D. Blaise, J. Sierra
Journal: Blood (2004)
Review of criterion-referenced standards for cardiorespiratory fitness: what percentage of 1 142 026 international children and youth are apparently healthy?
Authors: Justin J Lang, Mark S Tremblay, Francisco B Ortega, Jonatan R Ruiz, Grant R Tomkinson
Journal: British Journal of Sports Medicine (2017)

Purpose To identify criterion-referenced standards for cardiorespiratory fitness (CRF); to estimate the percentage of children and youth that met each standard; and to discuss strategies to help improve the utility of criterion-referenced standards for population health research. Methods A search of four databases was undertaken to identify papers that reported criterion-referenced CRF standards for children and youth generated using the receiver operating characteristic curve technique. A pseudo-dataset representing the 20-m shuttle run test performance of 1 142 026 children and youth aged 9–17 years from 50 countries was generated using Monte Carlo simulation. Pseudo-data were used to estimate the international percentage of children and youth that met published criterion-referenced standards for CRF. Results Ten studies reported criterion-referenced standards for healthy CRF in children and youth. The mean percentage (±95% CI) of children and youth that met the standards varied substantially across age groups from 36%±13% to 95%±4% among girls, and from 51%±7% to 96%±16% among boys. There was an age gradient across all criterion-referenced standards where younger children were more likely to meet the standards compared with older children, regardless of sex. Within age groups, mean percentages were more precise (smaller CI) for younger girls and older boys. Conclusion There are several CRF criterion-referenced standards for children and youth producing widely varying results. This study encourages using the interim international criterion-referenced standards of 35 and 42 mL/kg/min for girls and boys, respectively, to identify children and youth at risk of poor health—raising a clinical red flag.
The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma
Authors: Bibhusal Thapa, Adriana Salcedo, Xihui Lin, Marzena Walkiewicz, Carmel Murone, Malaka Ameratunga, Khashyar Asadi, Siddhartha Deb, Stephen Arthur Barnett, Simon Knight, Paul Mitchell, D. Neil Watkins, Paul C. Boutros, Thomas John
Journal: Journal of Thoracic Oncology (2017)
Two Distinct Precursors of Hematopoietic Stem Cells and Endothelial Progenitors Characterized by the PCLP1 Expression.
Authors: Izumi Onitsuka, Masaki Takeuchi, Tomoya Okabe, Yoshiko Kamiya, Ayami Hirata, Ichiro Yahara, Atsushi Miyajima
Journal: Blood (2005)
Risk Factors for Cerebral Vasculopathy in a Sickle Cell Disease Neonatal Cohort: A Prospective Study
Authors: Julie Sommet, Corinne Alberti, Nathalie Couque, Zinedine Haouari, Florence Missud, Laurent Holvoet, Ghislaine Ithier, André Baruchel, Malika Benkerrou
Journal: Blood (2014)
Fotemustine, Etoposide, Aracytin and Melphalan (FEAM), a Different Conditioning Regimen for Lymphoma Treatment with Autologous Hemopoietic Stem-Cell Transplantation
Authors: Maurizio Musso, Renato Scalone, Alessandra Crescimanno, Antonio Pinto, Gianpaolo Marcacci, Nicola Cascavilla, Potito Rosario Scalzulli, Nicola Di Renzo, Rosella Matera, Alfonso D’Arco, Francesco Lanza, Paolo Di Bartolomeo, Paolo Di Carlo, Tania Perrone, Carlo Bianchini
Journal: Blood (2008)
Clinical Efficacy of Daratumumab, Pomalidomide and Dexamethasone in Relapsed, Refractory Myeloma Patients: Utility of Retreatment with Daratumumab Among Refractory Patients
Authors: Ajay K Nooka, Nisha Joseph, Larry H Boise, Charise Gleason, Jonathan L. Kaufman, Sagar Lonial
Journal: Blood (2016)
A Novel Inosine Monophosphate Dehydrogenase Inhibitor VX-944 Overcomes Conventional Drug-Resistance in Multiple Mueloma Cells in the Bone Marrow Microenvironment.
Authors: Kenji Ishitsuka, Teru Hideshima, Makoto Hamasaki, Raje Noopur, Kumar Shaji, Hiroshi Yasui, Aldo M. Roccaro, Dharminder Chauhan, Klaus Podar, Yu-Zu Tai, Jugnu Jain, Kenneth C. Anderson
Journal: Blood (2004)
On adhering to Olympic guidelines on load in sport and risk of injury
Authors: João Brito
Journal: British Journal of Sports Medicine (2017)

I read with interest the latest consensus statements on ‘Load in Sport and Risk of Injury/Illness’ from the IOC.1 2 I am part of the Health and Performance Unit of the Portuguese Football Federation. My experience and that of my colleagues during last years Men’s Olympic Football Tournament in Brazil 2016 has prompted me to write this letter. The IOC consensus highlights current consensus on monitoring load to minimise negative health effects on athletes, as well as recommends that sports governing bodies must carefully consider competition formatting and calendars. We highlight the gap between these recommendations and the reality as we experienced at the 2016 Olympic Games. We hope that this case can start the process of helping governing bodies understand the challenges …
A Novel Anti-CD22 Immunotoxin, Moxetumomab Pasudotox: Phase I Study in Pediatric Acute Lymphoblastic Leukemia (ALL)
Authors: Alan S Wayne, Deepa Bhojwani, Lewis B. Silverman, Kelly Richards, Maryalice Stetler-Stevenson, Nirali N Shah, Sima Jeha, Ching-Hon Pui, Manuela Buzoianu, David J. FitzGerald, Robert J. Kreitman, Ramy Ibrahim, Ira Pastan
Journal: Blood (2011)
Impact of crizotinib on patient-reported symptoms and quality of life (QOL) compared with single-agent chemotherapy in a phase III study of advanced <i>ALK</i>+ non-small cell lung cancer (NSCLC).
Authors: Vera Hirsh, Fiona Helen Blackhall, Dong-Wan Kim, Benjamin Besse, Hiroshi Nokihara, Ji-Youn Han, Vanessa Roberts Tassell, Arlene Reisman, Shrividya Iyer, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2013)

8108 Background: PROFILE 1007 compared the efficacy and safety of the ALK inhibitor crizotinib (N=172) with that of standard-of-care chemotherapy (pemetrexed [PEM; N=99] or docetaxel [DOC; N=72]) in patients with advanced ALK+ NSCLC. The primary endpoint was progression-free survival. The main objective of our present post-hoc analyses was to compare patient-reported outcomes in the crizotinib arm with those of the DOC and PEM subgroups in the chemotherapy arm. Methods: Patient-reported outcomes were assessed at baseline, on day 1 of each cycle, and at the end of treatment using EORTC QLQ-C30 and lung cancer module QLQ-LC13. Higher scores (range 0−100) indicate higher symptom severity or better functioning/QOL. Time to deterioration (TTD) was defined as time from randomization to the earliest time with a ≥10-point increase from baseline for pain in chest, dyspnea, or cough and was compared between groups using an unstratified log-rank test. Repeated measures mixed-effects analyses were performed to compare change from baseline scores, with no adjustment for multiple comparisons. Results: Completion rates at baseline were ≥90% in each group and scores were well balanced. Crizotinib treatment was associated with a significantly longer TTD compared with PEM (median, 5.6 vs. 1.9 mo; HR, 0.66; 95% CI, 0.48−0.92; P=0.013) or DOC (median, 5.6 vs. 0.9 mo; HR, 0.37; 95% CI, 0.26−0.54; P&lt;0.0001). A significantly greater improvement from baseline was observed with crizotinib compared with either the PEM or DOC subgroups for global QOL (P&lt;0.01), cough (P&lt;0.001), dyspnea (P&lt;0.0001), pain in arm or shoulder (P&lt;0.0001), pain in chest (P&lt;0.0001), pain in other parts (P&lt;0.01), fatigue (P&lt;0.05), insomnia (P&lt;0.05), and pain (P&lt;0.0001). A significantly greater improvement was also observed with crizotinib compared with DOC for functioning (P&lt;0.05), alopecia (P&lt;0.0001), and hemoptysis (P&lt;0.0001). Conclusions: Crizotinib treatment showed a significantly greater improvement from baseline in key patient-reported lung cancer symptoms and global QOL compared with DOC and PEM, in addition to improved efficacy previously reported. Clinical trial information: NCT00932893.
Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting
Authors: Caterina Breitenstein, Tanja Grewe, Agnes Flöel, Wolfram Ziegler, Luise Springer, Peter Martus, Walter Huber, Klaus Willmes, E Bernd Ringelstein, Karl Georg Haeusler, Stefanie Abel, Ralf Glindemann, Frank Domahs, Frank Regenbrecht, Klaus-Jürgen Schlenck, Marion Thomas, Hellmuth Obrig, Ernst de Langen, Roman Rocker, Franziska Wigbers, Christina Rühmkorf, Indra Hempen, Jonathan List, Annette Baumgaertner, A Villringer, M Bley, M Jöbges, K Halm, J Schulz, C Werner, G Goldenberg, G Klingenberg, E König, F Müller, B Gröne, S Knecht, R Baake, J Knauss, S Miethe, U Steller, R Sudhoff, E Schillikowski, G Pfeiffer, K Billo, H Hoffmann, F-J Ferneding, S Runge, T Keck, V Middeldorf, S Krüger, B Wilde, K Krakow, C Berghoff, F Reinhuber, I Maser, W Hofmann, C Sous-Kulke, W Schupp, A Oertel, D Bätz, F Hamzei, K Schulz, A Meyer, A Kartmann, O'N Som, S-B Schipke, S Bamborschke
Journal: The Lancet (2017)
Hematoxylin in History—The Heritage of Histology
Authors: Faisal R. Ali, Guy E. Orchard, Rajeev Mallipeddi
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
Organ-Specific T Cell Receptor Repertoire in Target Organs of Murine Graft-Versus-Host after Haploidentical Bone Marrow Transplantation.
Authors: Yue Wen Fu, De Pei Wu, Feng Chen, Yu Feng Feng, Wei Rong Chong, Zi Ling Zhu, Ping Zhu
Journal: Blood (2007)
GATA2 May Contribute with EVI1 to the Leukemogenic Mechanism in Patients with 3q21q26 Rearrangements.
Authors: Iria Vazquez, Idoya Lahortiga, Nerea Marcotegui, Maria Jose Larrayoz, Carmen Vicente, Jesus Maria Hernandez, Jose Cervera, Maria Jesus Vidal, Jose A. Marquez, Maria Jose Calasanz, Maria Dolores Odero
Journal: Blood (2005)
Sleep Apnea
Authors: Shahrokh Javaheri, Ferran Barbe, Francisco Campos-Rodriguez, Jerome A. Dempsey, Rami Khayat, Sogol Javaheri, Atul Malhotra, Miguel A. Martinez-Garcia, Reena Mehra, Allan I. Pack, Vsevolod Y. Polotsky, Susan Redline, Virend K. Somers
Journal: Journal of the American College of Cardiology (2017)
Use of the 92-gene assay to identify tumor type and direct predictive biomarker testing in limited tissue specimens.
Authors: Theresa N. Operana, Brock Schroeder, Mark G. Erlander, Catherine A. Schnabel
Journal: Journal of Clinical Oncology (2013)

e19072 Background: Limited tissue availability from biopsies can limit comprehensive diagnostic testing and individualized care. The 92-gene assay is a gene expression-based cancer classifier that requires a minimal number of tumor cells (~300) and may improve the efficiency of tissue usage as a molecular complement to IHC in cases with limited diagnostic material. In this study, the reporting rate and utility of molecular classification in limited tissue cytology specimens, as well as the frequency of directed predictive biomarker testing were examined. Methods: Four hundred thirty eight FFPE cytopathology cases (ie, fine needle aspirates, pleural effusions, ascites) with indeterminate diagnosis where the 92-gene assay (CancerTYPE ID, bioTheranostics Inc.) was used in clinical care were included in the analysis. The 92-gene assay reporting rate and tissue availability to perform downstream biomarker testing were analyzed. Results: The 92-gene assay provided a molecular diagnosis in 86% (n=378) of cytopathology specimens submitted for diagnostic testing. Twenty-four distinct tumor types were predicted including: 9% lung (n=41), 8% urinary bladder (n=34), 8% pancreaticobiliary (n=34), 8% ovary (n=34), 7% gastroesophageal (n=32), 5% intestine (n=20), and 1% melanoma (n=5). In 66 patients with molecular diagnoses where reflex biomarker testing was applicable (lung, CRC, melanoma), 33% of cases had additional predictive biomarker testing performed, and 2 or more biomarker tests were performed on 15% of cases. The most common tests ordered were EGFR mutations (n=16), KRAS mutations (n=8), BRAF mutation (n=8), and ALK rearrangement (n=5). Conclusions: These findings demonstrate the suitability and high reporting rate of the 92-gene assay in limited tissue cytologic specimens and successful predictive biomarker testing in appropriate cases. With the growing number of molecularly-targeted therapies requiring predictive biomarker testing, use of the 92-gene assay may have increased utility in indeterminate cancer cases where limited tissue specimens are the only option for diagnosis and treatment planning.
Effects of the Genetic Background on the Myelofibrosis Induced by the GATA-1Low Mutation.
Authors: Anna Rita Migliaccio, Fabrizio Martelli, Barbara Panetta, Elena Alfani, Giovanni Migliaccio, Valentina Gatta, Angela Di Baldassarre, Alessandro Pancrazi, Costanza Bogani, Francesco Paoletti, Alessandro M. Vannucchi
Journal: Blood (2004)