tbuckley/cabot-search huggingface dataset:
Activity of lenalidomide in a phase II trial for T-cell lymphoma: Report on the first 24 cases
Authors: G. S. Dueck, N. Chua, A. Prasad, D. Stewart, D. White, R. vanderJagt, J. B. Johnston, A. Belch, T. Reiman
Journal: Journal of Clinical Oncology (2009)

8524 Background: Novel therapies are needed to improve outcomes in T-cell lymphomas. We report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas. Methods: Patients with relapsed and refractory T-cell lymphomas other than mycosis fungoides were prescribed oral lenalidomide (25mg daily) on days 1 to 21 of each 28 day cycle, with standardized dose reductions for toxicity. Treatment continued until disease progression, death or unacceptable toxicity. The primary endpoint was overall response rate, and secondary endpoints were complete and partial response rates, progression-free and overall survival (PFS, OS), and safety. The two-stage design allows for up to 40 patients. Results: At the time of this interim analysis, 24 patients were enrolled in this study and 23 were evaluable for response. The median age was 65 years. ECOG PS was 0–1 (n=15), 2 (n=7), 3 (n=2). The histology was peripheral T-cell unspecified (PTCL-u, n=10), angioimmunoblastic (n=7), anaplastic large cell (n=5), enteropathic T-cell (n=1) and hepatosplenic gamma/delta (n=1). Median number of prior therapies was 1 (range, 0–4), and three had prior autologous stem cell transplant. Four patients were previously untreated and not candidates for combination chemotherapy. Median time from completion of prior therapy to the start of lenalidomide was 8 months (range, 1–48 months). The overall response rate was 7/23 (30%); all were partial responses. Two patients had stable disease (SD) for ≥3 cycles. Responses were seen in anaplastic, angioimmunoblastic, and PTCL-u histologies. Median PFS was 96 days (range, 8–696 days). Median OS was 241 days (range, 8–696+ days). Among the 9 patients with SD or better, median PFS was 168 days and median OS has not yet been reached with 241–696 days of follow-up. The most common grade 4 adverse event was thrombocytopenia (33.3%). The most common grade 3 adverse events were neutropenia (20.8%), febrile neutropenia (16.7%), and pain NOS (16.7%). Conclusions: In relapsed and refractory T-cell lymphomas, oral lenalidomide monotherapy has clinical activity and toxicity is consistent with the known profile of lenalidomide. Further study of lenalidomide in these diseases is warranted. [Table: see text]
Abstract 2997: Vessel co-option in colorectal cancer liver metastases mediates resistance to VEGF-targeted therapy
Authors: Sophia Frentzas, Victoria L. Thompson, Peter B. Vermeulen, Shane Foo, Gina Brown, David Cunningham, Andrew R. Reynolds
Journal: Cancer Research (2014)

Abstract The purpose of this study is to: (1) examine whether vessel co-option is associated with a lack of response to anti-angiogenic therapy in advanced colorectal cancer patients, (2) identify whether inhibition of pathways associated with vessel co-option sensitizes to anti-angiogenic therapy in vivo. Sprouting angiogenesis is the process whereby new blood vessels are induced to sprout from existing vessels. The growth of metastatic tumors is considered to require sprouting angiogenesis. This hypothesis has driven the development and clinical application of vascular endothelial growth factor (VEGF) targeted agents, such as bevacizumab. However, responses to such agents in cancer patients, including metastatic colorectal cancer (CRC), are variable. It is not currently clear why this is the case and we have no way of selecting patients suitable for such therapies. Importantly, it is now evident that tumors can also utilize a number of putative ‘VEGF-independent’ angiogenesis mechanisms, the existence of which may limit the efficacy of VEGF-targeted therapy. One such mechanism is ‘vessel co-option,’ whereby tumors engulf existing local blood vessels as they invade into surrounding host tissue. Published studies have reported that this mechanism occurs in ∼28-30% of CRC liver metastases. Here we present data from a retrospective study of patients with CRC liver metatases that were treated with bevacizumab. We demonstrate that, in this patient cohort, the presence of vessel co-option in liver metastases was strongly associated with lack of response to bevacizumab. We also show that a similar result is observed in a mouse model of colorectal cancer liver metastasis. Interestingly, when we disable actin nucleation activity in colorectal cancer cells, vessel co-option is compromised and sensitivity to VEGF-targeted therapy is restored in vivo. These data demonstrate a potential role for vessel co-option as a negative predictive biomarker for anti-angiogenic therapy and also have consequences for the development of novel therapies for targeting tumor angiogenesis. Citation Format: Sophia Frentzas, Victoria L. Thompson, Peter B. Vermeulen, Shane Foo, Gina Brown, David Cunningham, Andrew R. Reynolds. Vessel co-option in colorectal cancer liver metastases mediates resistance to VEGF-targeted therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2997. doi:10.1158/1538-7445.AM2014-2997
Prevalence of Diabetes in the United States
Authors: William H. Herman, Amy E. Rothberg
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tumour necrosis factor-α-induced migration of human Langerhans cells: the influence of ageing
Authors: M. Bhushan, M. Cumberbatch, R.J. Dearman, S.M. Andrew, I. Kimber, C.E.M. Griffiths
Journal: British Journal of Dermatology (2002)

Journal Article Tumour necrosis factor‐α‐induced migration of human Langerhans cells: the influence of ageing Get access M. Bhushan, M. Bhushan Dermatopharmacology Unit, The Dermatology Centre, University of Manchester, and Search for other works by this author on: Oxford Academic Google Scholar M. Cumberbatch, M. Cumberbatch Syngenta Central Toxicology Laboratory, Alderley Edge, Macclesfield, Cheshire SK10 4TJ, U.K Search for other works by this author on: Oxford Academic Google Scholar R.J. Dearman, R.J. Dearman Syngenta Central Toxicology Laboratory, Alderley Edge, Macclesfield, Cheshire SK10 4TJ, U.K Search for other works by this author on: Oxford Academic Google Scholar S.M. Andrew, S.M. Andrew Department of Pathology, Hope Hospital, Salford, Manchester M6 8HD, U.K Search for other works by this author on: Oxford Academic Google Scholar I. Kimber, I. Kimber Syngenta Central Toxicology Laboratory, Alderley Edge, Macclesfield, Cheshire SK10 4TJ, U.K Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths C.E.M. Griffiths Dermatopharmacology Unit, The Dermatology Centre, University of Manchester, and Professor C.E.M.Griffiths. E‐mail: christopher.griffiths@man.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 1, 1 January 2002, Pages 32–40, https://doi.org/10.1046/j.1365-2133.2002.04549.x Published: 01 January 2002 Article history Accepted: 30 August 2001 Published: 01 January 2002
Impact of Nesiritide on Renal Function in Patients With Acute Decompensated Heart Failure and Pre-Existing Renal Dysfunction
Authors: Ronald M. Witteles, David Kao, Dianne Christopherson, Kelly Matsuda, Randall H. Vagelos, Donald Schreiber, Michael B. Fowler
Journal: Journal of the American College of Cardiology (2007)
Abstract 20027: Decellularized Aortic Allograft Vs. Pulmonary Autograft for Aortic Valve Replacement in Growing Sheep Model: Haemodynamic and Morphological Results After Implantation for 20 Months
Authors: Igor Tudorache, Karolina Theodoridis, Sarikouch Samir, Christoph Bara, Tanja Meyer, Klaus Höffler, Dagmar Hartung, Andres Hilfiker, Axel Haverich, Serghei Cebotari
Journal: Circulation (2014)

Introduction: Pulmonary autograft (PA) represents the substitute of choice for aortic valve replacement especially in children and young adults. Similarly, decellularized aortic valves (DAV) showed excellent midterm function when implanted into the systemic circulation. The aim of this study was to compare DAVs to pulmonary autografts after Ross procedure in the growing sheep model.

METHODS AND RESULTS: Aortic valve root replacement was performed in lambs (35-45kg) using either DAVs (n=5) or PAs (n=5) as in Ross procedure. Haemodynamics were investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and investigated by histology, immunohistochemistry, and transmission electron microscopy. The mean valve diameter increased from 14 to 23mm and from15 to 25mm in DAVs and PAs, respectively. Of all implanted grafts, only one PA exhibited moderate insufficiency at explantation. No significant differences were determined in mean transvalvular gradient between grafts of both groups at implantation and prior explantation. Cusps of all implants were soft, pliable without gross signs of degeneration. Repopulation with cells of DAVs occurred at the wall and cusp level without immune reaction. The endothelial lining was regularly restored.

Conclusion: Decellularized aortic allografts and pulmonary autografts provide adequate and comparable haemodynamics after aortic valve replacement in growing sheep. Furthermore, maintenance of valvular competence during enlargement of the valve ring indicates the capacity for physiological growth in both graft types.
950. FasL- Over-Expressing T Lymphocytes as Effector Cells in Anti-Prostate Cancer Gene Therapy
Authors: Katherine M. Finan, Greg Hodge, Ann M. Reynolds, Sandra J. Hodge, Mark D. Holmes, Andrew H. Baker, Paul N. Reynolds
Journal: Molecular Therapy (2004)

Lung cancer causes more cancer deaths than cancers related to colon, breast and prostate combined. More primary lung cancers are now diagnosed in former smokers than current smokers and this trend is set to continue. Despite advances in chemotherapeutic agents current treatment strategies are not effective enough in reducing the burden of disease, producing survival benefit or improving quality of life. There is no doubt that new treatment strategies are necessary to improve the outlook from this disease. Gene therapy exploits our expanding knowledge of the molecular basis of cancer using a number of cancer modifying techniques. The extracellular matrix (ECM) provides the scaffolding for all cells and is the environment in which all tissues and cells exist. In order for tissues to change their form the ECM must be degraded and the tissue remodelled. Matrix Metalloproteinases (MMPs) are the proteins that regulate ECM functions. Through a variety of complex mechanisms they control cell differentiation, proliferation and migration. The Tissue inhibitors of Metalloproteinases (TIMPs) are a family of multifunctional proteins named for their ability to inhibit MMPs. TIMP 3 also has the unique ability to directly induce apoptosis in certain tumour types. Hypothesis: In vitro delivery of AdCMVTIMP-3 induces apoptosis and cell death in lung cancer cells, that AdCMVTIMP-3 has a significant bystander effect and in vivo delivery of AdCMVTIMP-3 to implanted subcutaneous A549 tumours reduces tumour growth. Aims: To demonstrate the in vitro and in vivo apoptotic and cell killing effects of AdCMVTIMP-3. Methods: Lung cancer cells A549 were plated at known concentrations and then infected with adenoviral vectors carrying the genes for TIMP-1, -2 and 3. Changes consistent with apoptosis were observed at 48-66 hours post infection. A variety of flow cytometric analyses including Annexin V, Propidium Iodide, 7AAD and Single Stranded DNA confirm that AdCMVTIMP-3 induces apoptosis and cell death. Elevated Caspace, p53, BAX/Bcl2 and Fas levels show activation of the caspase cascade that regulates programmed cell death. MTT assays confirm reductions in cell numbers and demonstrate the significant bystander effects of AdCMVTIMP-3. In vivo analysis of A549 tumours implanted subcutaneously in nude mice shows delivery of AdCMVTIMP-3 inhibits tumour growth. TUNEL analysis of paraffin embedded tissue sections of these tumours shows evidence of increased numbers of apoptotic cells when compared to uninjected controls and those injected with control virus. Conclusion: Delivery of AdCMVTIMP-3 induces apoptosis and cell death in lung cancer cells and this can be demonstrated in vitro and in vivo.
Comment on Thomsen et al. Incretin-Based Therapy and Risk of Acute Pancreatitis: A Nationwide Population-Based Case-Control Study. Diabetes Care 2015;38:1089–1098
Authors: Mark M. Smits, Marcel H.A. Muskiet, Lennart Tonneijck, Daniël H. van Raalte
Journal: Diabetes Care (2015)

We read with great interest the article by Thomsen et al. (1), which is the latest study fueling the ongoing discussion on acute pancreatitis (AP) associated with incretin-based therapies. This controversy on drug safety started with conflicting animal and clinical data shortly after marketing approval of glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4I). Recently, regulatory authorities reviewed the available data and concluded no increased AP risk, yet they called for further studies (2). Thomsen et al. underlined this conclusion with results from the Danish Civil Registration System (CRS) database. In their case-control study, a history of incretin-based drug use was identified in 89 first-time hospitalization AP cases and 684 matched control subjects. …
Allergy is associated with suicide completion with a possible mediating role of mood disorder - a population-based study
Authors: P. Qin, P. B. Mortensen, B. L. Waltoft, T. T. Postolache
Journal: Allergy (2010)

To cite this article: Qin P, Mortensen PB, Waltoft BL, Postolache TT. Allergy is associated with suicide completion with a possible mediating role of mood disorder – a population-based study. Allergy 2011; 66: 658–664. Background: With increasing research suggesting a role of allergy on suicidality, this study, on a population level, delved into how allergy affects risk for suicide completion in the context of mood disorder and other factors. Methods: Based on the entire population of Denmark, we included 27 096 completed suicides and 467 571 live controls matched on sex and age with a nested case–control design. We retrieved personal information on hospital contacts for allergy and other variables from various Danish longitudinal registries and analyzed the data with conditional logistic regression. Results: We noted that 1.17% suicide victims, compared with 0.79% matched controls, had a history of hospital contact for allergy and that a history of allergy predicted an increased risk for suicide completion; however, the effect was confined to allergy that led to inpatient treatment (IRR: 1.59, 95% CI: 1.41–1.80). The increased risk was attenuated somewhat but remained significant when adjusted for personal psychiatric history and socioeconomic status. Meanwhile, we observed a nonsignificantly stronger effect in women than in men, and a significant age difference with a stronger effect for individuals at high ages. Moreover, we detected a significant interaction between allergy and mood disorder – even an antagonism effect of the two exposures. Allergy increased suicide risk only in persons with no history of mood disorder, whereas it eliminated suicide risk in those with a history of mood disorder. Conclusions: The findings support a link between allergy and suicidality, with a possible mediating role of mood disorder.
Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models
Authors: Mario Schiffer, Beina Teng, Changkyu Gu, Valentina A Shchedrina, Marina Kasaikina, Vincent A Pham, Nils Hanke, Song Rong, Faikah Gueler, Patricia Schroder, Irini Tossidou, Joon-Keun Park, Lynne Staggs, Hermann Haller, Sergej Erschow, Denise Hilfiker-Kleiner, Changli Wei, Chuang Chen, Nicholas Tardi, Samy Hakroush, Martin K Selig, Aleksandr Vasilyev, Sandra Merscher, Jochen Reiser, Sanja Sever
Journal: Nature Medicine (2015)
115. Genetic Fiber Mosaic Adenovirus Confers New Properties to Adenoviral Particles
Authors: Larisa Pereboeva, Svetlana Komarova, David T. Curiel
Journal: Molecular Therapy (2004)

Genetic capsid modifications of Ad vectors is one of the promising ways to tailor Ad virions as a gene transfer vector for the particular applications and introduce additional properties to the viral particles. Numerous approaches tested to date include capsid protein replacement, pseudotyping, mutagenesis, deletions and inserting targeting peptides. However, this promising strategy has some constrains in its practical realization mainly due to either structural incompatibility of desired genetic insertions with viral proteins or interference with viral life cycle. This limits number and nature of artificially incorporated targeting ligands and often hampers viral propagation. To address this issue we hypothesized that mosaic virus (having two distinct fibers in one viral particle) would allow an increase in the number of sites on the Ad capsid permitting structural modifications. To test feasibility of this approach we first generated mosaic adenovirus genetically encoding two fibers: wild type and  fiber – Fiber-Fibritin (FF). We confirmed incorporation of FF in mosaic viral particles by Western blot. Binding experiments demonstrated that fiber-mosaic Ad retained binding ability of the wt fiber while also attained new binding properties provided by the second fiber. Next we considered more drastic modifications of the adjunct fiber and genetically fused Fiber-Fibritin to a biotin acceptor peptide (PSTCD, P. shermanii transcarboxylase domain, 77 aa). Presence of biotin on adjunct fiber may confer new properties to the viral particle, which can be exploited for detection, purification or retargeting. As one practical approach this strategy allows conjugating fiber-mosaic virus with any streptavidin/avidin-bearing peptides or proteins as targeting adaptors. We have rescued and propagated the virus Ad FF-PSTCD, having both fibers incorporated in the virion: wt fiber and FF- PSTCD. We confirmed incorporation of FF-PSTCD in mosaic viral particles by Western blot. Next, we demonstrated the ability of this fiber to be metabolically biotinylated in 293 cells. As an example of the practical utility of such viral modifications, we investigated the ability of the biotinylated fiber-mosaic Ad to target infection to the EGF receptor (EGFR) overexpressed on cancer cell lines. As a molecular bridge to cross-link biotinylated fiber with EGFR we used a recombinant bispecific fusion protein, where EGF sequence was genetically fused to core-streptavidin. Our findings indicate that Ad FF-PSTCD gained significant infectivity advantage in an EGF-retargeting approach compare to wt virus. Enhanced infectivity of fiber-mosaic Ad provided by EGF-related targeting was not abolished by blocking with recombinant Ad5 knob, while wild type infection at the same experimental conditions was blocked. Experiments are on going to test ligands with other specificities as streptavidin-fusion conjugates in our retargeting approach.
Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain
Authors: Keishi Fujio, Tetsuya Nosaka, Tetsuo Kojima, Toshiyuki Kawashima, Takashi Yahata, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Kazuhiko Yamamoto, Takashi Nishimura, Toshio Kitamura
Journal: Blood (2000)
Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device
Authors: Krischan D. Sjauw, Thomas Konorza, Raimund Erbel, Paolo L. Danna, Maurizio Viecca, Hans-Heinrich Minden, Christian Butter, Thomas Engstrøm, Christian Hassager, Francisco P. Machado, Giovanni Pedrazzini, Daniel R. Wagner, Rainer Schamberger, Sebastian Kerber, Detlef G. Mathey, Joachim Schofer, Annemarie E. Engström, Jose P.S. Henriques
Journal: Journal of the American College of Cardiology (2009)
1048. Long-Term Regulated Gene Expression in Non-Human Primates Using a Single Non-Recombinogenic AAV Vector
Authors: Victor M. Rivera, Lori Berk, Scott Wardwell, Hao Tang, Guang-ping Gao, Rebecca L. Grant, James M. Wilson, Tim Clackson
Journal: Molecular Therapy (2004)

Gene therapy is a promising route for the delivery of secreted therapeutic proteins but pharmacologic control of gene expression will generally be required for optimal safety and efficacy. We have developed a regulation system in which expression of a target gene is made dependent on a transcription factor (TF) that is activated by rapamycin or AP22594, a derivative with substantially reduced immunosuppressive activity. To minimize the potential for immunogenicity in a clinical setting the system has been built exclusively from human proteins.
Guidance on the use of biological agents in the treatment of oral mucosal disease
Authors: I. O’Neill
Journal: British Journal of Dermatology (2010)

Journal Article Guidance on the use of biological agents in the treatment of oral mucosal disease Get access I. O’Neill I. O’Neill de l’immeuble 3, Centre d’Affaires Poincaré, 3 Rue Poincaré, 06000, Nice, France E‐mail: iain.oneill@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1410–1411, https://doi.org/10.1111/j.1365-2133.2010.09704.x Published: 01 June 2010
Main Street. The Story of Carol Kennicott.
Authors: Sinclair Lewis
Journal: JAMA (1920)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal