tbuckley/cabot-search huggingface dataset:
Role of induction chemotherapy in the multimodal management of locally advanced epithelial sinonasal cancer
Authors: P. Bossi, E. Orlandi, R. Granata, P. Quattrone, P. Battaglia, D. Lombardi, L. Pala, M. Barbàra, P. Nicolai, P. Castelnuovo, M. Guzzo, L. Locati, C. Resteghini, S. Alfieri, M. Imbimbo, N.A. Iacovelli, G. Calareso, C. Bergamini, L. Licitra
Journal: Annals of Oncology (2015)
A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer
Authors: T. K. Joensuu, G. Joensuu, P. Nokisalmi, C. Reddy, J. Isola, M. Ruutu, M. Kouri, P. Kupelian, A. Hemminki
Journal: Journal of Clinical Oncology (2009)

e16079 Background: We estimated the safety and tolerability of 250 mg gefitinib q.d. given concurrently with three- dimensional conformal radiotherapy (3D-CRT) in patients with non-metastatic prostate cancer (PC). Methods: 42 patients with T2/T3N0M0 PC were treated in a single centre, non-randomized study (study code ZD1839/IL0118). PSA&lt;20 and good performance status (WHO 0–1) were required. Adjuvant or neo-adjuvant hormonal treatments were not allowed. 250 mg gefitinib q.d. was started one week before and lasted for the duration of radiation therapy. 50.4 Gy (1.8 Gy/day) of 3D-CRT was administered to the tumor, prostate and seminal vesicles, followed by a 22 Gy booster (2 Gy/day) for a 72.4 Gy total dose. EGFR expression, presence of EGFRvIII and activated pEGFR were studied. Levels of serum TNF, IL-1 α and IL-6 were also evaluated. Results: Maximum tolerated dose was not reached in phase I (12 patients) and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication and 12 (28.6%) prematurely discontinued because of adverse events. Dose-limiting toxicities were recorded in 16 (38.1%) patients, the most common of which was grade 3–4 transaminase increase (6 patients). After median follow-up of 38 months nobody had died of PC. The estimated PSA-free survival rate at 4 years (Kaplan-Meier) was 97%, hormone-free survival 91% and overall survival 87%. These figures compared favourably with matched, non-randomized patients treated with radiation only. Data on biochemical analyses will be presented. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity in non-metastatic PC. A randomized study is being discussed for evaluating the efficacy of the approach. [Table: see text]
243. Pre-Clinical Development of Lentiviral Gene Therapy for X-Linked Severe Combined Immunodeficiency
Authors: Valentina Poletti, Sabine Charrier, Samia Martin, Arianna Moiani, Céline Sagrère, Sandrine Ferrand, Matthias Hebben, Fang Zhang, Karen Buckland, Michael Rothe, Alex Schambach, Bobby H. Gaspar, Adrian Thrasher, Fulvio Mavilio
Journal: Molecular Therapy (2015)

X-linked severe combined immunodeficiency (SCID-X1, OMIM #300400) is caused by mutations in the gene encoding the interleukin-2 receptor γ-chain (IL2RG) resulting in a lack of response to common γ-chain-dependent cytokines, absence of T- and NK-cell development, and impairment of B-cell function. Previous SCID-X1 clinical trials based on MLV-based retroviral vectors expressing the IL2RG gene successfully restored immunity in most patients, demonstrating the efficacy of the gene therapy despite the occurrence on insertional T leukemias in some patients. To overcome these side effects, we decided to developed a SIN lentiviral-vector (LV) carrying a codon-optimized human IL2RG cDNA under the control of the human EF1α-S promoter, including a mutated WPRE. The vector was VSV-G-pseudotyped and produced by a new manufacturing process based on quadri-transfection of suspension-adapted 293T cells grown in bioreactors in serum-free conditions, purified by ion-exchange chromatography and concentrated by tangential-flow filtration. The activity of the LV was tested in vitro by transduction of the IL2RG-deficient EDR7 human T-cell line and cord blood-derived or peripheral blood mobilized CD34+ hematopoietic progenitors. The LV reconstituted normal levels of surface IL2RG in ED7R cells at an average VCN of 2 and 90% transduction efficiency. Transduction of CD34+ cells resulted in a VCN of 2.8±0.7 at a transduction efficiency of 82±9% by CFC assay with no impact on viability and cloning efficiency. Induction of aberrant splicing of genes harboring LV proviruses was assayed in EDR7 cell clones in which LV integrations were characterized by LM-PCR and sequencing. The LV caused abnormal splicing at low frequency between upstream exons and constitutive or cryptic proviral splice sites located in the LTR or at internal positions. To test the therapeutic efficacy and potential genotoxicity of the LV, we transplanted lethally-irradiated IL2RG-deficient mice with BM-derived, lin- cells transduced at 72±15% efficiency with a VCN of 2.5±1.1. Transplanted mice are being tested at 3 and 6 months post-transplantation for restoration of T- and B-cell function. Integration site analysis will be performed to monitor LV integration and analyze the clonal repertoire of transduced BM and peripheral blood cells. Potential genotoxicity is also assayed by an in vitro immortalization (IVIM) study on primary cells. These studies will enable a multicenter phase-I/II/registration clinical trial aimed at establishing the safety and clinical efficacy of lentiviral vector-mediated gene therapy for SCID-X1.
Association Between Hospitalization for Infection and Suicide
Authors: William T. Regenold
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
In vitro sensitivity to 5-FU and gemcitabine in pancreatic cancer.
Authors: J. Franko, M. M. Bilimoria, S. Chalikonda, D. A. Iannitti
Journal: Journal of Clinical Oncology (2011)

312 Background: Gemcitabine and 5-fluorouracil (5-FU) represent the mainstay of chemotherapeutic options for pancreatic cancer. Currently, approximately 40% of patients with pancreatic cancer receive chemotherapy. Relapse is common after resection and adjuvant therapy, and response rates are low in patients with advanced/metastatic disease. The purpose of this study was to describe the prevalence of in vitro drug sensitivity or resistance to these agents in pancreatic cancer and explore the clinical implication of in vitro assessment. Methods: From August 2006 to January 2010, 74 specimens from patients with primary/metastatic pancreatic cancer were tested for response to gemcitabine, 5-FU, and their combination using an in vitro chemosensitivity assay (ChemoFx, Precision Therapeutics, Pittsburgh, PA). Tumors were classified as sensitive or resistant based on in vitro dose response curves. Results: Thirty-four of the 74 tumor specimens (46%) exhibited in vitro chemosensitivity to gemcitabine, 5-FU, or their combination. Fourteen tumors (19%) were sensitive to gemcitabine, and 12 (16%) to 5-FU. Of the 60 patient specimens resistant to gemcitabine, 4 (7%) were sensitive to 5-FU. Conversely, of the 62 specimens resistant to 5-FU, 6 (10%) were sensitive to gemcitabine. Eight of the 74 specimens (11%) were sensitive to both gemcitabine and 5-FU and 56 (76%) were resistant to both agents. Of these 56 specimens, 16 (29%) showed sensitivity to the gemcitabine/5-FU combination. Conclusions: The ChemoFx data indicates a high (76%) in vitro resistance rate to traditional chemotherapy. In vitro chemosensitivity to gemcitabine only partially overlaps with that of 5-FU and the gemcitabine/5-FU combination. Thus, tumors resistant to one drug, were not necessarily resistant to the other and vice versa. Further correlation with clinical outcomes is needed to determine the clinical efficacy of the ChemoFx assay. [Table: see text]
The Efficacy and Safety of VP-16 and G-CSF as a Mobilization Regimen Prior to Autologous Stem Cell Transplantation (ASCT) for Patients (Pts) with Multiple Myeloma (MM) and Lymphoma.
Authors: William A. Wood, Julia Whitley, Dominic T Moore, Jonathan S Serody, Don A. Gabriel, James M. Coghill, Robert Irons, Thomas C. Shea
Journal: Blood (2009)
Abstract 1448: Dynamic chromatin modification by tumor secreted Hsp90 modulates EMT and tumor invasion
Authors: Krystal D. Nolan, Michael W. Hance, Omar E. Franco, Simon W. Hayward, Jennifer S. Isaacs
Journal: Cancer Research (2015)

Abstract Tumor metastasis is the main cause of prostate cancer lethality. Pathological reactivation of the developmental genetic program epithelial to mesenchymal (EMT) is associated with increased tumorigenesis and invasion, and is considered a primary culprit for tumor dissemination. Hallmarks of EMT include upregulation of the core transcription factors Zeb and Snail, concomitant with suppression of the junctional protein E-cadherin. Overexpression of the epigenetic repressor EZH2, a histone methyltransferase, is also implicated in EMT activation. Although these molecular events are well known to trend with cancer progression, a paucity of knowledge exists regarding identification of the clinically-relevant upstream triggers capable of setting these events into motion. We recently demonstrated that tumor secreted extracellular heat shock protein 90 (eHsp90) initiates EMT events in prostate cancer cells. Moreover, we reported the presence of surface Hsp90 in human prostatectomy specimens, an event highly correlated with elevated expression of a subset of EMT transcripts. The present study reveals novel mechanistic aspects of eHsp90 action. We define an epigenetic function for eHsp90 as a significant regulator of EZH2 expression and activity. This eHsp90-EZH2 axis was found to govern a majority of eHsp90's pro-EMT activity in vitro, and was essential for E-cadherin suppression and tumor invasion in vivo. Upon further investigation, it was revealed that eHsp90 sustained ERK activation. This eHsp90-ERK pathway was required for the increased expression of EZH2, as well as for its directed recruitment to the E-cadherin promoter. Moreover, eHsp90-ERK signaling augmented the epigenetic landscape of Zeb and Snail towards a profile permissive for transcriptional activation. Hence, our findings indicate that eHsp90-ERK signaling has profound effects upon key drivers of cancer progression via the concerted action of epigenetic modulation of EMT effectors and increased EZH2 expression. Collectively, these data support a model wherein tumor eHsp90 functions as an upstream rheostat for EZH2 expression and activity to orchestrate mesenchymal properties and coincident aggressive behavior. Importantly, our findings suggest that eHsp90 may be a clinically relevant instigator in the transition from localized to invasive disease. Citation Format: Krystal D. Nolan, Michael W. Hance, Omar E. Franco, Simon W. Hayward, Jennifer S. Isaacs. Dynamic chromatin modification by tumor secreted Hsp90 modulates EMT and tumor invasion. [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 1448. doi:10.1158/1538-7445.AM2015-1448
Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases
Authors: A Hinks, J Bowes, J Cobb, H C Ainsworth, M C Marion, M E Comeau, M Sudman, B Han, M L Becker, J F Bohnsack, P I W de Bakker, J P Haas, M Hazen, D J Lovell, P A Nigrovic, E Nordal, M Punnaro, A M Rosenberg, M Rygg, S L Smith, C A Wise, V Videm, L R Wedderburn, A Yarwood, R S M Yeung, S Prahalad, C D Langefeld, S Raychaudhuri, S D Thompson, W Thomson
Journal: Annals of the Rheumatic Diseases (2016)

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides.Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed.We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA.The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.
Cord Blood (CB) CD34+ and CD3+ Cells with Decreasing Levels of Their Mitochondrial Potential Are Not Detectable with 7-AAD, Have Impaired Function and Ultrastructural Morphology Characteristic of Early Apoptosis.
Authors: Maria S. Albano, Andromachi Scaradavou, Susanne Heck, Cladd E. Stevens, Pablo Rubinstein
Journal: Blood (2007)
Colorectal Cancer Screening Comparative Effectiveness—Clinical Trials Are Not Always the Answer
Authors: Chyke A. Doubeni
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
PP-008 Survival of<i>Escherichia coli</i>in monocytic cells in Crohn's disease: evidence of reduced killing capacity
Authors: B N Hudspith, K Blackie, N B Rayment, T Elliott, J Brostoff, J Hermon-Taylor, J D Sanderson
Journal: Gut (2010)

<h3>Introduction</h3> Whist the exact cause of Crohn9s disease (CD) remains unclear, an innate defect in the handling of intracellular bacteria appears to be involved. Evidence for this comes from 1. genome wide association studies implicating a role for genes involved in bacteria-immune cell interactions including NOD-2 and the autophagy related genes, ATG16L1 and IRGM, 2. an observed defect in phagocyte recruitment and 3. the consistent demonstration of viable <i>E coli</i> within lamina propria macrophages in CD. It is not known if this latter observation is due to increased uptake of <i>E coli</i> or a failure to achieve effective phagolysosomal killing of bacteria once within the cell. <h3>Methods</h3> To examine phagocytosis and oxidative burst activity of phagocytic cells in peripheral blood of 16 healthy individuals and 16 patients with CD. Phagocytic activity was assessed by the number of cells taking up fluorescently tagged <i>E coli</i> (Phagotest) and the potential role of defective reactive oxygen radical (ROR) production involved in bacterial killing (Bursttest). This is measured by the conversion of non-fluorescent dihydrorhodamine 123 to the fluorescent rhodamine 123 by ROR9s. The leucocytes were challenged with three strains of <i>E coli</i>, a heat killed sample, a laboratory strain (K12) and a strain isolated from a patient with CD. Results were obtained using florescent markers measured by flow cytometery. <h3>Results</h3> Using the phagotest, to measure the uptake of bacteria no difference was seen between CD and controls and did not vary according to strain of <i>E coli</i> used. However, although the number of monocytes expressing ROR9s was similar in both groups, their was a significantly level of ROR9s produced in cells from CD compared to controls when viable bacteria were used (<i>E coli</i> K12: control 98.5±7.4 vs CD 68.1±13.2, p=0.04, and the CD isolate: control cells 101.1±7.4 vs CD 59.2±12.2, p=0.010). No difference was seen in the granulocytes between CD and controls for either phagocytosis or ROR<i>9</i>s. <h3>Conclusion</h3> The ability of monocytes from CD patients to engulf <i>E coli</i> appears to be normal. However, there is good evidence of an impaired capacity to kill these bacteria as measured by reduced levels of ROR<i>9</i>s. These results points to either an inability to complete the process of phagolysosome formation or defects in the enzyme pathways involved in formation of reactive oxygen products that are induced by phagocytosis and support the concept of impaired innate immunity in CD.
152. Tumor Inhibition by Using Chitosan:siRNA PDGFR-β in Breast Cancer Model of Rat
Authors: Jülide Akbuğa, Suna Ozbas Turan, Emine Salva, Naziye Ozkan, Levent Kabasakal, Saadet Alan
Journal: Molecular Therapy (2016)

Platelet-derived-growth factors (PDGFs) may represent a novel target in human cancer because they regulate many cellular processes, including cell proliferation, transformation, apoptosis and angiogenesis. PDGF-D's exert their cellular effects by two receptors PDGFR-α and PDGFR-β. Moreover PDGF ligands and receptors are proto-oncogenes that can be activated by various types of alternatives in cancer cells. Breast cancer is the most common and fatal type of cancer. The PDGF pathway is essential in tumor angiogenesis. It is known that the expression of PDGF receptors is altered and upregulated in breast cancer. Delivery is very important for success in gene therapy. Among the different non-viral gene delivery system, chitosan has very useful properties as a gene carrier. In this study; we investigated the effect of chitosan:siRNA complexes on tumor angiogenesis in breast tumor models of rats. Firstly chitosan:siRNA complexes (1/5-1/20 rate) targeting to PDGFR-β were prepared and characterized in vitro. Transfection efficiency of these nanoplexes in breast cancer cells such MCF-7, MDA-MB-231 and MDA-MB-435 was assayed. In in vitro transfection studies, 54%-65% of PDGFR-β inhibition was measured. Then these chitosan:siRNA complexes were injected intratumorally to tumor bearing Sprague Dawley rats. After tumor reached to constant size, complexes (20/1) were injected (40µg siRNA) and tumor volumes were measured periodically. After sacrification of animals, tissue and blood samples were taken and investigated histologically and immuno-histochemically. Expression levels of PDGFR-β determined by ELISA, mRNA levels were measured by RT-PCR also. Nanoplexes having 207 ± 3.5 nm size and 14.2 mV surface charge were used in this study. Tumor volume of nanoplex treated rats decreased at 92.49% at the end of the experiment (28th day). After free siRNA treatment, however, tumor volume increased very slowly until 21 days (68.1 % of decreasing value) then went up fastly. RT-PCR, Western-blot studies and immuno-histochemical data showed similarity with tumor volume measurements. Similar IFN response with tumor (untreated) was obtained after nanoplex administration. In conclusion, chitosan can be complexed with siRNA targeting PDGFR-β and chitosan:siRNA PDGFR-β nanocomplexes may be useful alternative in the treatment of breast cancer. The receptors of PDGF may be also suitable target in breast cancer.
Isoform-Specific Expression and Feedback Regulation of E Protein TCF4 Control Dendritic Cell Lineage Specification
Authors: Lucja T. Grajkowska, Michele Ceribelli, Colleen M. Lau, Margaret E. Warren, Ioanna Tiniakou, Sandra Nakandakari Higa, Anna Bunin, Hans Haecker, Leonid A. Mirny, Louis M. Staudt, Boris Reizis
Journal: Immunity (2016)