tbuckley/cabot-search huggingface dataset:
609. Transduction of the Central Nervous System with the LTR1 Lentiviral Backbone
Authors: Rajvinder Karda, John R. Counsell, Conrad A. Vink, Dany P. Perocheau, Suzanne M.K. Buckley, Joanne Ng, Simon N. Waddington, Steven J. Howe
Journal: Molecular Therapy (2016)

A novel HIV-1-based lentiviral vector has been generated that eliminates 1.7kb of wild-type HIV-1 elements from the vector provirus. This vector, known as LTR1, potentially offers several advantages over current lentiviral technology, such as increased transgene-carrying capacity, resistance to remobilisation in HIV-1 particles and a reduced risk of splicing interactions with host genes. In this study we investigated the persistence and strength of LTR1-derived expression within the central nervous system (CNS). We began by developing LTR1 vectors containing the spleen-focus forming virus (SFFV) promoter driving either green fluorescent protein (GFP) (LTR1-SFFV-GFP), or a bicistronic luciferase-GFP construct (LTR1-SFFV-Luc-GFP). Both LTR1 vector preparations were pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G) and administered intracranially to newborn outbred CD1 mice. Those that received the LTR1-SFFV-Luc-GFP virus were imaged continually by whole body bioluminescence imaging. From this, we observed long term luciferase expression within the CNS for 32 days post-administration, at which point the mice were sacrificed for further analysis. Mice receiving the LTR1-SFFV-GFP virus were euthanized at day 35 and the brain tissues were collected, sectioned and stained for GFP by free-floating immunohistochemistry, which showed GFP-positive neurons predominately within the cortex and hippocampus. In this research, we demonstrated long-term expression within the CNS, specifically the cortex and the hippocampus, after a single neonatal administration of the LTR1 virus. We have therefore highlighted its potential use as a gene therapy vector for neurological disorders. This, combined with LTR1's potential to incorporate large transgenes, highlights a possible application in gene therapy of channelopathies, which would benefit from viral delivery of the relatively large sodium ion channels.
PTU-034 Expression of connective tissue growth factor by human intestinal myofibroblasts and effect of rho-kinase inhibition
Authors: E Stirling, K R Hughes, Y R Mahida
Journal: Gut (2010)

<h3>Introduction</h3> Connective tissue growth factor (CTGF) has been implicated in the development of fibrosis in different organs, including stricture formation in Crohn9s disease. As a profibrotic mediator, CTGF acts downstream and together with transforming growth factor β (TGF-β). Expression of TGF-β has previously been shown to be altered in myofibroblasts isolated from mucosal samples affected by inflammatory bowel disease. Rho-kinase is a downstream mediator of RhoA, a GTP-binding protein that is believed to regulate a number of myofibroblast functions. The aims of this study were to investigate (i) the expression of CTGF by human intestinal myofibroblasts isolated from mucosal samples obtained from different individuals and (ii) the effect of the Rho-kinase inhibitor Y-27632 on CTGF expression by intestinal myofibroblasts. <h3>Methods</h3> Myofibroblasts were isolated from normal colonic mucosal samples (obtained from operation resection specimens) and established in pure culture. Myofibroblasts were cultured in medium containing 0.1% or 10% fetal calf serum (FCS). CTGF transcript expression was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and expression of protein (in cell lysates) by Western blot analysis. Following incubation with Y-27632 (final concentration 100 μM), changes in myofibroblast cell morphology, expression of CTGF and programmed cell death (analysis of the sub-G1 region of the cell cycle by flow cytometry) were studied. <h3>Results</h3> Studies by RT-PCR showed that when grown in 10% FCS, intestinal myofibroblast cultures from 5 mucosal tissue donors expressed CTGF transcript. Expression of CTGF protein was confirmed by western blot analysis of intestinal myofibroblasts grown in 10% FCS (n=7 donors). By contrast, when cultured in 0.1% FCS, only 2 out 5 donors expressed CTGF protein (0.1% FCS vs 10% FCS: p&lt;0.03). Exposure to Y-27632 led to change in morphology to spindle-shaped cells, with all the myofibroblasts affected by 24 h. When cultured for 24 h with 10% FCS, Y-27632 led to a reduction in expression of CTGF protein by intestinal myofibroblasts isolated from 6 donors. However, there was no significant difference in the number of myofibroblasts undergoing programmed cell death between those cultured in medium only, compared to cells exposed to Y-27632 (events in sub-G1 region of cells cycle: 203.8 (SEM 51.62) vs 393.0 (64.91), p=0.10). <h3>Conclusion</h3> 1. Myofibroblasts isolated from normal human colonic mucosal samples are capable of expressing CTGF. 2. The Rho-kinase inhibitor Y-27632 reduces expression of CTGF protein by colonic myofibroblasts. 3. The Rho-kinase pathway may be a suitable therapeutic target in stricturing Crohn9s disease.
Preferences for short versus long - term androgen deprivation in prostate cancer survivors
Authors: D. Wilke, M. Krahn, P. Warde, A. Bezjak, G. Tomlinson, R. Rutledge, A. Detsky
Journal: Journal of Clinical Oncology (2004)

4620 Background: RTOG 92–02 has demonstrated that long-term androgen deprivation prolongs cause –specific survival in patients with locally advanced prostate cancer by 3.4 %. However, androgen deprivation decreases sexual function, reduces bone mass, and health - related quality of life. Methods: Patients with prostate cancer who received radiotherapy were presented with a scenario of Locally Advanced Prostate Cancer. We determined the minimally required increment in survival (MRIS) to accept LTAD (as opposed to STAD), using the Probability trade –off (PTO) technique. Utilities for impotence and osteoporosis associated with LTAD were determined using the Time trade –off (TTO) technique. The participants' current erectile function and prostate cancer –specific health –related quality of life were assessed using the International Index of Erectile Function (IIEF), and the Patient –Oriented Prostate Utility scale (PORPUS), respectively. Results: Sixty-seven patients were interviewed. The median age of participants was 72 (range 52 - 82). All participants were willing to trade survival in order not to have to undergo LTAD, compared to STAD. The median MRIS for prostate cancer –specific survival was 9.5%. Thirty percent of participants did not desire LTAD even if they were offered a 100% prostate cancer –specific survival. The median MRIS for prostate cancer –specific survival without an overall survival gain was 13% (the maximum trade off possible in the scenario), the mean being 9.75% [8.7 to 10.8%]. Median time willing to be traded off for impotence associated with LTAD was 2.5 years, corresponding to a median utility of 0.84. Median time willing to be traded off for osteoporosis associated with LTAD was 4.5 years, corresponding to a median utility of 0.72. Multivariable linear regression of the MRIS for prostate cancer –specific survival revealed that age, IIEF sexual domain score, and having had bypass procedures were independent predictors of the MRIS for prostate cancer –specific survival. Conclusions: Prostate cancer patients are willing to accept decreased survival in order to avoid the quality of life consequences of long-term androgen deprivation. No significant financial relationships to disclose.
In Vivo Bioluminescence Imaging to Study the Contribution of TNF-TNFR Interactions on Immune and Parenchymal Cells to Tumor Cell Progression in a Syngenic Mouse Model
Authors: Martin Chopra, Simone S Riedel, Viktoria von Krosigk, Carina A Bäuerlein, Christian Brede, Ana-Laura Jordan-Garrote, Stefanie Donat, Miriam Ritz, Axelle Degla, Hermann Einsele, Harald Wajant, Andreas Beilhack
Journal: Blood (2011)
Macrophage NADPH Oxidase Activation and ROS Production Is Positively Regulated By Shp2 Phosphatase Function
Authors: XingJun Li, Charles Goodwin, Zhenyun Yang, Sarah C Nabinger, Briana Richine, Gordon Chan, Helmut Hanenberg, Hiroaki Ohnishi, Takashi Matozaki, Jamel El Benna, Gen-Sheng Feng, Benjamin Neel, Rebecca J. Chan
Journal: Blood (2014)
Metaphase Cytogenetic Abnormality (CA) Subtypes in Multiple Myeloma (MM) Treated with Front Line Total Therapy (TT) Protocols TT1, TT2, TT3, TT4 and TT5
Authors: Frits van Rhee, Jeffrey R Sawyer, Saad Z Usmani, Sarah Waheed, Christoph Heuck, Alan Mitchell, Antje Hoering, Bart Barlogie
Journal: Blood (2012)
The Mystery of the Christmas Tree
Authors: Walter H. C. Burgdorf, Gerd Plewig, Dan Lipsker, Leonard J. Hoenig
Journal: JAMA Dermatology (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 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
Efficient Non-Viral Transfection of Mouse and Human Embryonic Stem Cells.
Authors: Zwi N. Berneman, Jeremy P. Brown, Sjaak Van der Sar, Dave Van den Plas, Lena Van den Eeden, Dirk R. Van Bockstaele, Philippe G. Jorens, Viggo F. Van Tendeloo, Joseph Merregaert, Prim B. Singh, Peter Ponsaerts
Journal: Blood (2004)
Abstract 4575: Açaí intake reduces the aberrant crypt foci development in a colitis-associated carcinogenesis model in male Wistar rats
Authors: MARIANA F. FRAGOSO, GUILHERME R. ROMUALDO, CLAUDIA H. PELLIZZON, LUIS F. BARBISAN
Journal: Cancer Research (2015)

Abstract Colorectal cancer is a main cause of cancer death in the western world. In Brazil, it is the third more common neoplasia in both men and women (INCA, 2014). In our previous study (Fragoso et al., Food Chem Toxicol., 2013), we showed that spray-dried açaí (Euterpe oleraceae Mart.) pulp intake retarded the development of colon cancer in male Wistar rats. Therefore, the objective of this research was to evaluate the potential protection of dietary freeze-dried açaí pulp using a chemically-induced colon carcinogenesis and colitis-associated model in male Wistar rats. The animals were randomly distributed into four groups: G1, DMH [dimethylhydrazine] + TNBS [2,4,6-trinitrobenzene sulfonic acid] + basal diet; G2, DMH + TNBS + basal diet with 5% açai pulp; G3, DMH + TNBS + basal diet with 7.5% açai pulp; G4, DMH + TNBS + basal diet with 0.2% of NAC [N-acetylcysteine]. The acute colitis was induced with the administration of 10 mg of TNBS dissolved in 0.25 ml 50% ethanol (v/v) by means of a Teflon cannula inserted 8 cm into the anus. At the end of the 25th week, animals were sacrificed for evaluation of Aberrant Crypt Foci (ACF) in the colon. Unsenctioned and fixed colons were analyzed for total aberrant crypt (AC) and total ACF and ACF multiplicity under methylene blue staining. The results were analyzed by ANOVA followed by post hoc Tukey test. A significant reduction in total ACF and AC for G2 when compared to G1 (p ≤0.001) was seen. Regarding the ACF multiplicity, it was observed a significant reduction in ACF with 4-10 aberrant crypts for G2 and G4 and for ACF with &amp;gt;10 aberrant crypts for G2-G4 groups in relation to the G1 group (p = ≤0.001, respectively). Also, it was observed a significant reduction in the number of total AC in the distal colon from the G2 and G4 groups compared to G1 group (p = 0.003) and in the medial colon from the G2 group compared to G1 group (p = 0.016). These results suggest that açaí intake may reduce the number of AC and ACF and the number of ACF with more than four aberrant crypts in this chemically-induced colon carcinogenesis and colitis-associated model in rats. Citation Format: MARIANA F. FRAGOSO, GUILHERME R. ROMUALDO, CLAUDIA H. PELLIZZON, LUIS F. BARBISAN. Açaí intake reduces the aberrant crypt foci development in a colitis-associated carcinogenesis model in male Wistar rats. [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 4575. doi:10.1158/1538-7445.AM2015-4575
Abstract 155: LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation
Authors: Pratirodh Koirala, Yin Yuan MO
Journal: Cancer Research (2015)

Abstract The human genome expresses a large number of long non-coding RNAs (lncRNAs), however, little is known about their physiological functions or their role in cancer for the vast majority of these lncRNAs. In the present study, we identified a set of lncRNAs that were differentially expressed in breast cancer tissues as compared to normal tissue. Among them is AK023948 which is up-regulated in breast cancer tissue and in breast cancer cell lines. Ectopic expression of AK023948 in breast cancer MCF-7 cells promotes proliferation and anchorage independent cell growth along with activation of AKT phosphorylation. On the other hand, knockdown or knockout of AK023948 in MCF-7 cells reduces the proliferation of cells and phosphorylation of AKT. Furthermore, there is a positive correlation between AK023948 and pAKT expression in breast cancer tissue microarray. To determine the underlying mechanism of AK023948-mediated activation of AKT, we performed RNA precipitation assays using biotin-labeled AK023948 RNA probe, followed by PAGE analysis, and detected a unique protein band by silver staining. Mass spectrometry analysis identified it as ATP dependent RNA helicase A (RHA/DHX9) which was confirmed by Western blot and RNA immunoprecipitation (IP), respectively. Co-IP indicated that DHX9 interacts with p85PI3K regulatory subunit. Further characterization revealed that p85-DHX9 interaction is essential for stability of p85α and AKT phosphorylation. Together, these results suggest that AK023948 may function as an oncogenic lncRNA in breast cancer and thus, it may serve as a novel target for breast cancer therapy. Citation Format: Pratirodh Koirala, Yin Yuan MO. LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation. [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 155. doi:10.1158/1538-7445.AM2015-155
Phase I trial: Pretransplant targeting of multiple myeloma stem cell (MMSC) with armed activated T cells (aATC).
Authors: Z. S. Al-Kadhimi, A. Thakur, E. Tomaszewski, M. H. Abidi, J. A. Zonder, V. Ratanatharathorn, L. J. Ayash, A. Deol, P. Steele, K. Myers, J. P. Uberti, L. G. Lum
Journal: Journal of Clinical Oncology (2011)

e18570^ Background: Relapse continues to be a challenge affecting patient’s survival in multiple myeloma. Chemoresistance of myeloma stem cell MMSC (CD138-CD20+) remains an obstacle to complete disease eradication. Methods: We utilized the presence of CD20 antigen on MMSC to target them with ex vivo expanded anti-CD3 activated autologous T cells armed with anti-CD3 x anti-CD20 bispecific antibody (aATC), to determine whether anti-MMSC immunity could be induced. Patients were given two infusions of 1010 aATC 1 week apart after completing myeloma induction therapy and prior to autologous stem cell transplant ASCT. Results: Twelve patients (pts) were enrolled. Nine pts have received their aATC, ASCT, are evaluable for safety, and immune correlative studies. These nine pts are alive at a median 159 days after ASCT (115-360). Two pts have relapsed. There were no dose-limiting toxicities (DLT) associated with ATC infusions. One pt developed catheter related blood clot. Infusional grade II/III toxicities included: 8 hypotension, 16 chills, and 1 fever. All pts engrafted between days (11–23). Flirgrastim was used only if engraftment was delayed beyond day 15. Immune testing suggests that aATC infusions induced anti myeloma immune responses in 7/9 pts prior to ASCT. Conclusions: Infusions of aATC to target CD20 pre ASCT seems to be feasible and safe. Further studies to determine the efficacy of this approach are needed. Pt No. Age Sex Durie Salmon- stage Disease status@ ASCT Stem cells collected X 106/ kg Neutrophil engraftment (days)* Relapse/progression post ASCT Post transplant survival (days)* 1 66 F I A VGPR 6 11 Relapse 360 2 42 M II A CR 7.6 13 0 319 3 55 F III A PR 10.3 17 0 248 4 49 F III A PR 14 23 Relapse 187 5 59 M III A CR 7.9 17 0 150 6 41 F III A VGPR 7.2 13 0 159 7 66 M III A PR 20.9 21 0 122 8 67 F I A PR 8.2 12 0 117 9 66 F II B PR 8 18 0 115 * Post ASCT Abbreviations: CR, complete remission; VGPR, very good partial response; PR, partial response.
Abstract A51: Notch4 acts as an oncogenic signal in pancreatic tumorigenesis
Authors: Wanglong Qiu, David D. Suh, Natasha M. Tsay, Simona Chadi, Adam R. Chambers, Peter A. Sims, Carrie J. Shawber, Jan Kitajewski, Helen E. Remotti, Gloria H. Su
Journal: Cancer Research (2016)

Abstract The Notch signaling network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between adjacent cells. The Notch family receptor and its signaling pathways are involved in the development of numerous tissues in multicellular organisms. Recent studies from our Acvr1bflox/flox;LSL-KrasG12D;Pdx1-Cre mice suggest that Notch4 plays an oncogenic role in dictating cell fate and contributes to pancreatic tumorigenesis, particularly in the development of pancreatic intraductal papillary mucious neoplasms (IPMNs). The perinuclear localization of the activated Notch4 (but not other Notch members) intracellular domain (ICD) in the apical cytoplasm of neoplastic cells appeared to be associated with the expansion of the IPMN lesions. The unique role of Notch4 signaling pathway in IPMN development was also confirmed by unbiased RNA-Seq analyses. The deletion of Notch4 in the p16flox/flox;LSL-KrasG12D;Pdx1-Cre mice prolonged survival, further supporting its oncogenic role in pancreatic tumorigenesis. Citation Format: Wanglong Qiu, David D. Suh, Natasha M. Tsay, Simona Chadi, Adam R. Chambers, Peter A. Sims, Carrie J. Shawber, Jan Kitajewski, Helen E. Remotti, Gloria H. Su.{Authors}. Notch4 acts as an oncogenic signal in pancreatic tumorigenesis. [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 A51.
Plasma Level of NT-Pro-BNP In Children with Sickle Cell Disease Is Associated with Degree of Anemia and Left Ventricular Measures: The PUSH Study
Authors: Gregory J. Kato, Craig Sable, Gregory Ensing, Niti Dham, Caterina Minniti, Alan Remaley, Andrew Campbell, Manuel Arteta, Sohail Rana, Deepika Darbari, Mehdi Nouraie, Onyinye Onyekwere, Mark Gladwin, Oswaldo Castro, Victor R. Gordeuk
Journal: Blood (2010)
Abstract 5345: Enhanced inhibition of PC-3 xenograft prostate tumor growth by combination of green tea and quercetin with docetaxel
Authors: Piwen Wang, Susanne Henning, David Heber, Jaydutt Vadgama
Journal: Cancer Research (2015)

Abstract Chemotherapy with docetaxel (Doc) is a standard treatment for metastatic and castration-resistant prostate cancer. However, the development of chemoresistance and its side effects limit the clinical success of Doc. Previously we demonstrated that the combined use of natural products green tea (GT) and quercertin (Q) with Doc synergistically enhanced the anti-proliferative effect in androgen-independent prostate cancer PC-3 cells. The objective of the present study was to confirm the combined effect of GT, Q and Doc in xenograft prostate cancer mouse models and determine underlying mechanisms. Male severe combined immunodeficiency (SCID) mice (n = 10 per group) were inoculated with 5×105 PC-3 cells subcutaneously. When tumors reached a size of about 100mm3 the intervention started. Mice were administered with GT+Q, Doc 5mg/kg (LD), GT+Q+LD Doc, Doc 10mg/kg (HD) or control. The concentration of GT polyphenols in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.4%. Doc was given through tail vein once a week for 4 weeks. There was a nonsignificant inhibition of tumor growth by GT+Q or LD Doc alone compared to control. However the combination treatment with GT+Q+LD Doc significantly inhibited the tumor growth by 62% compared to LD Doc alone after 7 weeks intervention. The combined effect was comparable to that by HD Doc treatment. Western blot analysis demonstrated a significantly increased ratio of Bax to Bcl-2 protein expression by GT+Q+LD Doc treatment compared to GT+Q or LD Doc. ELISA analysis of blood samples demonstrated that the combination treatment significantly decreased the blood concentrations of several growth factors, including VEGF, EGF, TGF-β, FGF-β, and TNF-α compared to GT+Q or LD Doc alone. A liver toxicity evaluation revealed that the blood alanine aminotransferase (ALT) level was significantly elevated with HD Doc treatment compared to control, while not changed by other groups. Further mechanistic investigations using protein array and tissue microarray assays are ongoing. This study provides a promising regimen by combining GT and Q with Doc to enhance chemotherapeutic effect in advanced prostate cancer in a less toxic manner. The results warrant future clinical trials to confirm the combined effect of the mixture in humans. Citation Format: Piwen Wang, Susanne Henning, David Heber, Jaydutt Vadgama. Enhanced inhibition of PC-3 xenograft prostate tumor growth by combination of green tea and quercetin with docetaxel. [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 5345. doi:10.1158/1538-7445.AM2015-5345