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Kushagra Verma, Senthil T Nathan, Carly D Comer, Baron Lonner, Suken A Shah
STUDY DESIGN: Prospective Analysis OBJECTIVE.: This study aims to: 1) establish a baseline for the SRS-22 in South East Asia and 2) evaluate the influence of patient demographics on the SRS-22. SUMMARY OF BACKGROUND DATA: Previous studies have established a baseline for the SRS-22 in the US and described the impact of patient demographics. While the SRS-22 is used internationally, limited normative data is available. METHODS: After approval from the local hospital and school board, 1200 adolescents (age 10-18) were asked to anonymously complete the SRS-22 in English...
October 24, 2016: Spine
Paulina J Paszkiewicz, Simon P Fräßle, Shivani Srivastava, Daniel Sommermeyer, Michael Hudecek, Ingo Drexler, Michel Sadelain, Lingfeng Liu, Michael C Jensen, Stanley R Riddell, Dirk H Busch
The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface...
October 17, 2016: Journal of Clinical Investigation
Linan Wang, Ning Ma, Sachiko Okamoto, Yasunori Amaishi, Eiichi Sato, Naohiro Seo, Junichi Mineno, Kazutoh Takesako, Takuma Kato, Hiroshi Shiku
Carcinoembryonic antigen (CEA) is a cell surface antigen highly expressed in various cancer cell types and in healthy tissues. It has the potential to be a target for chimeric antigen receptor (CAR)-modified T-cell therapy; however, the safety of this approach in terms of on-target/off-tumor effects needs to be determined. To address this issue in a clinically relevant model, we used a mouse model in which the T cells expressing CEA-specific CAR were transferred into tumor-bearing CEA-transgenic (Tg) mice that physiologically expressed CEA as a self-antigen...
2016: Oncoimmunology
Mark W Lowdell, Amy Thomas
Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres...
October 17, 2016: British Journal of Haematology
Noelle V Frey, David L Porter
Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patients with relapsed and refractory B-cell neoplasms, including those with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas. Notably, durable responses have been observed in patients who had not undergone consolidative stem cell transplant, a finding that correlates with reports of T-cell persistence and B-cell aplasia in studies of anti-CD19 treatment in vivo...
October 15, 2016: Oncology (Williston Park, NY)
Daniel H Li, James B Whitmore, Wentian Guo, Yuan Ji
Recent trials of adoptive cell therapy (ACT), such as the chimeric antigen receptor T (CAR-T) cells therapy, have demonstrated promising therapeutic effects for cancer patients. A main issue in the product development is to decide appropriate dose of ACT. Traditional phase 1 trial designs for cytotoxic agents explicitly assume that toxicity increases monotonically with dose levels and implicitly assume the same for efficacy to justify dose escalation. ACT usually induces rapid responses, and the monotonic dose-response assumption is unlikely to hold due to its immunobiological activities...
October 14, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Leonardo Solaini, Bambang T Atmaja, Prabhu Arumugam, Robert R Hutchins, Ajit T Abraham, Satyajit Bhattacharya, Hemant M Kocher
BACKGROUND: We aim to evaluate the prognostic value of preoperative and postoperative inflammatory systems in patients who had undergone surgery for colorectal liver metastases, focusing our analysis on the role of C-reactive protein-to-albumin ratio (CAR) and Glasgow prognostic score (GPS). METHODS: A total of 194 patients were enrolled onto this study. Demographics, tumor-related variables, preoperative and postoperative (day 1) inflammatory variables were analyzed as potential prognostic factors...
October 11, 2016: International Journal of Surgery
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
Antoine Tanet, Annik Hubert-Barthelemy, Graciela C Crespin, Nicolas Bodeau, David Cohen, Catherine Saint-Georges
INTRODUCTION: Individuals with autism spectrum disorder (ASD) who also exhibit severe-to-moderate ranges of intellectual disability (ID) still face many challenges (i.e., less evidence-based trials, less inclusion in school with peers). METHODS: We implemented a novel model called the "Developmental and Sequenced One-to-One Educational Intervention" (DS1-EI) in 5- to 9-year-old children with co-occurring ASD and ID. The treatment protocol was adapted for school implementation by designing it using an educational agenda...
2016: Frontiers in Pediatrics
Risa Sawaki, Johanna Kreither, Carly J Leonard, Samuel T Kaiser, Britta Hahn, James M Gold, Steven J Luck
Schizophrenia clearly involves impairments of attention, but the precise nature of these impairments has been difficult to determine. One possibility is that the deficit in attention is a secondary consequence of a deficit in goal maintenance. However, recent research suggests that people with schizophrenia (PSZ) actually focus attention more strongly on objects containing goal-relevant features. To test these competing hypotheses, we recorded event-related potentials (ERPs) from PSZ (N = 20) and healthy control subjects (HCS; N = 20) while they looked for a particular target color at fixation and tried to ignore lateral distractors that sometimes matched the target color (target-color distractors)...
October 6, 2016: Journal of Abnormal Psychology
Preeti Sharma, David M Kranz
Adoptive T-cell therapies have shown exceptional promise in the treatment of cancer, especially B-cell malignancies. Two distinct strategies have been used to redirect the activity of ex vivo engineered T cells. In one case, the well-known ability of the T-cell receptor (TCR) to recognize a specific peptide bound to a major histocompatibility complex molecule has been exploited by introducing a TCR against a cancer-associated peptide/human leukocyte antigen complex. In the other strategy, synthetic constructs called chimeric antigen receptors (CARs) that contain antibody variable domains (single-chain fragments variable) and signaling domains have been introduced into T cells...
2016: F1000Research
Michele Moschetta, Yawara Kawano, Klaus Podar
Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents...
2016: Cancer Treatment and Research
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
Michael Boice, Darin Salloum, Frederic Mourcin, Viraj Sanghvi, Rada Amin, Elisa Oricchio, Man Jiang, Anja Mottok, Nicolas Denis-Lagache, Giovanni Ciriello, Wayne Tam, Julie Teruya-Feldstein, Elisa de Stanchina, Wing C Chan, Sami N Malek, Daisuke Ennishi, Renier J Brentjens, Randy D Gascoyne, Michel Cogné, Karin Tarte, Hans-Guido Wendel
The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors...
October 6, 2016: Cell
Lorenz Jahn, Renate S Hagedoorn, Dirk M van der Steen, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
CD22 is currently evaluated as a target-antigen for the treatment of B-cell malignancies using chimeric antigen receptor (CAR)-engineered T-cells or monoclonal antibodies (mAbs). CAR- and mAbs-based immunotherapies have been successfully applied targeting other antigens, however, occurrence of refractory disease to these interventions urges the identification of additional strategies. Here, we identified a TCR recognizing the CD22-derived peptide RPFPPHIQL (CD22RPF) presented in human leukocyte antigen (HLA)-B*07:02...
September 26, 2016: Oncotarget
Juliano Fernandes-da-Silva, Carlo Castagna, Anderson Santiago Teixeira, Lorival José Carminatti, Luiz Guilherme Antonacci Guglielmo
The aim of this study was to examine the relationship between the peak velocity derived from the Carminatti Test (T-CAR) (PVT-CAR) and physical match performance in young soccer players. Thirty-three youth soccer players were recruited from 2 non-professional clubs. Friendly matches and small-sided game were performed. Physical match demands were assessed using Global Positioning System (GPS) technology. On a separate occasion, the players were submitted to the T-CAR. Players were categorised into 3 groups based on their T-CAR performance: Low (PVT-CAR ≤ P33), Intermediate (P33 > PVT-CAR < P66) and High (PVT-CAR ≥ P66)...
August 10, 2016: Journal of Sports Sciences
Omar Wever-Pinzon, Stavros G Drakos, Stephen H McKellar, Benjamin D Horne, William T Caine, Abdallah G Kfoury, Dean Y Li, James C Fang, Josef Stehlik, Craig H Selzman
BACKGROUND: The number of centers with left ventricular assist device (LVAD) research programs focused on cardiac recovery is very small. Therefore, this phenomenon has been reported in real-world multi-center registries as a rare event. OBJECTIVES: This study evaluated the incidence of cardiac recovery with an a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a recovery predictive model. METHODS: The study included LVAD recipients registered in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)...
October 4, 2016: Journal of the American College of Cardiology
David R Okada, Paco E Bravo, Tomas Vita, Vikram Agarwal, Michael T Osborne, Viviany R Taqueti, Hicham Skali, Panithaya Chareonthaitawee, Sharmila Dorbala, Garrick Stewart, Marcelo Di Carli, Ron Blankstein
No abstract text is available yet for this article.
September 28, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
C J DeSelm, M Hamieh, M Sadelain
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
M A Cortez, A B Korngold, D R Valdecanas, H G Caruso, S Niknam, L Cooper, J W Welsh
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
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