tbuckley/cabot-search huggingface dataset:
424. Myd88/TLR Signaling Is Required for Immunotherapy-Mediated Glioblastoma Regression
Authors: James F. Curtin, Gwendalyn D. King, Marianela Candolfi, Chunyan Liu, Kathrin S. Michelsen, Moshe Arditi, Tamer M. Fakhouri, Begonya Comin-Anduix, Antoni Ribas, Pedro R. Lowenstein, Maria G. Castro
Journal: Molecular Therapy (2006)

Glioblastoma multiforme (GBM) is the most common type of brain tumor and is a leading cause of mortality with mean patient survival 6-12 months following diagnosis. We have recently shownthat combined treatment of glioma bearing rats with Ad-Flt3L and Ad-TK+GCV dramatically improved survival in an intracranial syngeneic rat model. Ad-Flt3L encodes human soluble fms-like tyrosine kinase 3 ligand (Flt3L) and stimulates dendritic cell proliferation and improves antigen presentation. Ad-TK expresses herpes simplex type I-thymidine kinase and selectively kills rapidly dividing cells when used in combination with the non-toxic prodrug ganciclovir (GCV). We now show that combined treatment with Ad-TK and Ad-Flt3L improves long-term survival in C57BL/6 mice bearing syngeneic intracranial GL26 tumors when all individual therapies completely fail (p<0.001). Survival is not improved in RAG1 deficient mice (RAG1-/-), deficient for mature B and T cells, or mice deficient for either CD4+ and CD8+ cells, implicating that both CD4 and CD8 T cells play a critical role in tumor regression. Tumor antigen Trp2 is expressed by GL26 cells and clonal expansion of Trp2(180-188) reactive T cells was determined using ELISPOT, MHC I – Trp2(180-188) tetramers and T cell proliferation assays following treatment with Ad-Flt3L and Ad-TK+GCV. Furthermore, Ad-Flt3L and Ad-TK did not improve survival in tumor bearing Myd88- or TLR2-deficient mice, indicating that TLR2 and Myd88 signaling was involved in the development of effective anti-tumor immune responses. In summary, combined treatment with Ad-Flt3L and Ad-TK+GCV improves survival in a large syngeneic intracranial tumor model in mice. This was dependent on the establishment of tumor antigen specific T cell anti tumor immune responses that was dependent, in turn, on TLR2 signaling via the adapter protein Myd88.
Canadian GPs believe that media health reporting could be better
Authors: David Spurgeon
Journal: BMJ (1999)

<h3>Introduction</h3> Despite evidence of health inequalities for adults with intellectual disability (ID) there has yet to be a comprehensive review of how well hospital services are meeting the needs of children and young people (CYP) with ID and their families. We do not know how relevant existing recommendations and guidelines are to CYP, whether these are being applied in the paediatric setting or what difference they are making. Evidence of parental dissatisfaction with the quality, safety and accessibility of hospital care for CYP with ID exists. However, the extent to which their experience differs from parents of CYP without ID is not known and the views and experiences of CYP with ID have not been investigated. We will compare how services are delivered to, and experienced by CYP aged 5–15 years with and without ID and their families to see what inequalities exist, for whom, why and under what circumstances. <h3>Methods and analysis</h3> We will use a transformative, mixed methods case study design to collect data over four consecutive phases. We will involve CYP, parents and hospital staff using a range of methods; interviews, parental electronic diary, hospital and community staff questionnaire, patient and parent satisfaction questionnaire, content analysis of hospital documents and a retrospective mapping of patient hospital activity. Qualitative data will be managed and analysed using NVivo and quantitative data will be analysed using parametric and non-parametric descriptive statistics. <h3>Ethics and dissemination</h3> The study will run from December 2015 to November 2018. We have Health Authority Approval (IRAS project ID: 193932) for phase 1 involving staff only and ethical and Health Authority Approval for phases 2–4 (IRAS project ID: 178525). We will disseminate widely to relevant stakeholders, using a range of accessible formats, including social media. We will publish in international peer-reviewed journals and present to professional, academic and lay audiences through national and international conferences.
Abstract 1692: Dalantercept, an ALK1 inhibitor of angiogenesis, in combination with cisplatin inhibits tumor growth in a xenograft model of squamous cell carcinoma of the head and neck
Authors: Marat Alimzhanov, Michael Lee, Nicolas Solban, Scott Pearsall, Susan Pandya, Matthew L. Sherman, Ravindra Kumar
Journal: Cancer Research (2014)

Abstract Activin receptor-like kinase 1 (ALK1) is a key regulator of angiogenesis and vascular morphogenesis. ALK1 and its co-receptor endoglin are selectively expressed on the surface of activated endothelial cells during angiogenesis. Bone morphogenetic proteins (BMP) 9 and 10 are ligands that bind to ALK1 and induce activation of the heteromeric receptor complex, phosphorylation of SMAD1/5/8, and upregulation of specific genes involved in the maturation stage of angiogenesis, such as Id-1 and TMEM100. In particular, BMP9 expression is upregulated in a majority of squamous cell carcinomas of the head and neck (SCCHN). Dalantercept is an ALK1 extracellular domain-Fc fusion protein that binds BMP9 and BMP10 with high affinity and antagonizes ALK1 signaling in vivo resulting in defective vascular maturation and inhibition of tumor growth in preclinical models. In a completed Phase 1 trial in patients with advanced, refractory solid tumors dalantercept demonstrated signs of clinical activity in a variety of patients, including two of three patients with SCCHN who achieved either an objective response or prolonged stable disease. A Phase 2 trial of dalantercept as monotherapy in recurrent/metastatic SCCHN patients who have had prior platinum-based chemotherapy is currently ongoing. Based upon the single agent activity of both dalantercept and cisplatin in SCCHN, we tested the feasibility of the combination of cisplatin plus dalantercept in a mouse model of SCCHN. Combination treatment of dalantercept plus cisplatin showed significant tumor growth inhibition (TGI) in the RPMI2650 xenograft model (59% TGI on day 30) which was significantly better than either cisplatin (35% TGI, p= 0.0077) or dalantercept (32% TGI, p=0.0002) alone. No additional toxicity was observed in the combination treatment group compared to cisplatin monotherapy group. These data suggest that combination of dalantercept plus cisplatin may result in enhanced clinical activity and supports prospective evaluation in patients with SCCHN. Citation Format: Marat Alimzhanov, Michael Lee, Nicolas Solban, Scott Pearsall, Susan Pandya, Matthew L. Sherman, Ravindra Kumar. Dalantercept, an ALK1 inhibitor of angiogenesis, in combination with cisplatin inhibits tumor growth in a xenograft model of squamous cell carcinoma of the head and neck. [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 1692. doi:10.1158/1538-7445.AM2014-1692
Abstract 2002: A novel candidate metastasis-associated protein, MAP40, differentially expressed in highly metastatic breast cancer cells reveals an essential role in tumor metastasis
Authors: Mijin Kim, Seong-Jin Kim
Journal: Cancer Research (2014)

Abstract Metastasis is the underlying cause of death in the majority of patients with breast cancer who succumb to their disease, but the fundamental mechanisms remain poorly understood. Here we have found a novel candidate of metastasis-associated protein, MAP40, which is highly expressed membrane protein in the metastatic breast cancer cell lines. Using the public microarray datasets, we also found that MAP40 is significantly increased in the basal type of breast tumors compared to the luminal subtype. We undertook the lentivirus-based system to functionally silence MAP40 gene in basal-like breast cancer cell lines. Knockdown of MAP40 results in a significant reduction of cell migration and invasiveness as well as suppression of anchorage-independent growth in basal-like breast cancer cells. Additionally, depletion of MAP40 induces E-cadherin expression, while integrin β1 protein level is suppressed. Together with results from studies in animal models suggest that MAP40 may promote tumor formation and direct metastasis of breast cancer in vivo. Ongoing studies to find interacting partners and downstream genes will allow us to further understand its mechanism in metastasis. This work was supported by a National Research Foundation grant of Korea (2009-0081756) funded by the Korea government. Citation Format: Mijin Kim, Seong-Jin Kim. A novel candidate metastasis-associated protein, MAP40, differentially expressed in highly metastatic breast cancer cells reveals an essential role in tumor metastasis. [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 2002. doi:10.1158/1538-7445.AM2014-2002
Effects of an Antireticular Cytotoxic Serum on the Brown-Pearce Carcinoma of the Rabbit
Authors: David Movitz, Otto Saphir, Alfred A. Strauss
Journal: Cancer Research (1949)

Administration of a reticulo-endothelial tissue antiserum, previously known to affect reticulo-endothelial tissue directly by in vitro tissue culture, was followed by definite effects on the degree of malignancy of the Brown-Pearce carcinoma in vivo . Reticulo-endothelial cytotoxic serum may be given in doses that apparently produce stimulation instead of a cytotoxic effect. The cytotoxic effect of the serum on the Brown-Pearce carcinoma was indirectly and presumably well demonstrated in the first three series by producing definitely enhanced malignancy. A dose too minute to have an effect was observed in Series V and VI. Finally, a mild cytostimulatory effect was obtained with one-tenth the cytotoxic dose, given at 7- to 10-day intervals, as indirectly indicated by the resulting tumor inhibition.
Chemopreventive effects of clotrimazole on B[a]P-induced carcinogenesis in the hamster cheek pouch model
Authors: Jimi L. Brandon, Miriam Rogel, Claudio Conti, John Digiovanni, Adrian M. Senderowicz, Irma B. Gimenez-Conti
Journal: Cancer Research (2005)

2465  The present study was carried out to examine the putative chemopreventive effects of clotrimazole on the hamster cheek pouch carcinogenesis model. This model of oral carcinogenesis has been widely used in chemoprevention studies (Shklar, G., et al, Prog Exp Tumor Res, 24, 269-282, 1979; Gimenez-Conti, I.B., et al, Mol Carcinog, 5, 259-263, 1992). Clotrimazole is a widely used synthetic antimycotic. Recently it became clear that clotrimazole has antiproliferative effects. Benzo[a]pyrene (B[a]P) is a ubiquitously distributed environmental carcinogen. Using B[a]P and a complete carcinogenesis protocol we have been able to produce pre-cancerous (leukoplakia-like) lesions at 16 weeks of treatment and squamous cell carcinomas at 20 weeks of treatment. These lesions are primarily endophytic and resemble those that develop in human oral mucosa. In the present study we are examining the long-term chemopreventive effects of clotrimazole on the hamster cheek pouch carcinogenesis model. The right cheek pouch of each male Syrian Hamster was treated topically 3 times per week with 50mM clotrimazole followed 30 minutes later by 2% B[a]P. The animals were sacrificed at 32-weeks and the right cheek pouches were harvested for histological and immunohistochemical evaluation. Upon histological evaluation the lesions were classified as pre-cancerous lesions, carcinomas in situ, or squamous cell carcinomas. A very significant decrease (∼80%) in tumor incidence was observed in clotrimazole-treated animals, when compared to the B[a]P-treated positive control group. Moreover, there was a significant decrease in pre-cancerous lesions (30%) and carcinomas in situ (55%) when compared with the control. Initial immunohistochemistry was performed to assess proliferation (anti-BrdU), p53 protein accumulation (anti-p53), and apoptosis (Tunel). Clotrimazole-treated animals demonstrated a significant decrease in proliferation (40%), p53 expression (58%), and apoptosis (58%), compared to the positive control group. These results indicate significant chemopreventive activity of clotrimazole in the B[a]P-induced carcinogenesis in the hamster cheek pouch model. Based on this exciting data, it is reasonable to test this hypothesis in human trials of patients afflicted with leukoplakia and/or patients at risk for aerodigestive tract malignancies.
Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas
Authors: Graeme Hodgson, Jeffrey H. Hager, Stas Volik, Sujatmi Hariono, Meredith Wernick, Dan Moore, Donna G. Albertson, Daniel Pinkel, Colin Collins, Douglas Hanahan, Joe W. Gray
Journal: Nature Genetics (2001)
Clinical Effectiveness and Primary Care, by Mark Baker, Neal Masirey, Simon Kirk
Authors: C. Silagy
Journal: BMJ (1997)

Mark Baker, Neal Masirey, Simon Kirk Radcliffe Medical Press, £18.50, pp 180 ISBN 1 857 75129 9

There are a number of contemporary issues that seem to dominate healthcare reform in most Western countries. One is the growing emphasis on clinical effectiveness, and another is the increasingly influential role of primary care as the setting in which healthcare services are delivered. The relation between clinical effectiveness and primary care is a complex one.

Implementing …
Abstract 304: Conversion of Ventricular Fibrillation to an Organized Rhythm Without a Defibrillator
Authors: Mikkel T Steinberg, Jan-Aage Olsen, Bjorn Bendz, David Persse, Fritz Sterz, Michael Lozano, Marc A Brouwer, Marc Westfall, Chris M Souders, Reinhard Malzer, Pierre M van Grunsven, David T Travis, E Brooke Lerner, Lars Wik
Journal: Circulation (2013)

Background: Reports of pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) converting to an organized rhythm without defibrillator use are rare. We wish to report a series of such cases in the randomized Circulation Improving Resuscitation Care (CIRC) trial comparing outcome between integrated AutoPulse CPR (iA-CPR) and Manual-CPR (M-CPR) in patients with out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology. Methods: Defibrillator ECGs were studied to determine rhythm one minute after defibrillation attempts and rhythm immediately before the next defibrillation attempt. Rhythms were categorized as VF, pulseless VT, asystole or an organized rhythm. Organized rhythms were classified as either pulseless electrical activity (PEA) or as return of spontaneous circulation (ROSC) if accompanied by a steep increase in EtCO2, trans-thoracic impedance showing typical “dips,” and a detectable pulse. Results: In 1603 patients with analyzable date and a shockable rhythm there were 13 cases of VF/VT (10/3) conversions to PEA or ROSC during periods with external chest compressions without defibrillation attempts. In eight of the 10 VF cases chest compressions converted VF to PEA (5 iA-CPR vs 3 M-CPR) and in two to ROSC (2 iA-CPR vs 0 M-CPR). With VT one case converted to PEA (M-CPR ) and two to ROSC (2 iA-CPR vs 0 M-CPR). Examples will be presented. Conclusion: This study documents that conversion of VF or VT to an organized rhythm during CPR without electrical assistance is possible but rare.
Resurrecting Treatment Histories of Dead Patients—Reply
Authors: Peter B. Bach, Deborah Schrag, Colin B. Begg
Journal: JAMA (2005)

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
Abstract 10998: Estimated Surgical Risk and Anatomical Compatibility for MitraClip Intervention in Patients With Severe Mitral Regurgitation According to Valve Disease Etiology
Authors: Yoram Agmon, Itai Gofman
Journal: Circulation (2014)

Background: Percutaneous mitral valve repair using the MitraClip technology was originally introduced to treat degenerative (myxomatous) mitral regurgitation (DMR), but it is currently mostly used in patients (pts) with functional (ischemic) MR (FMR). We examined whether this approach was justified, based on surgical risk and valve anatomy. Methods: Consecutive pts with severe MR who were hospitalized at a tertiary care medical center were identified and their clinical records and echocardiographic studies were reviewed. Surgical risk was estimated using the Society of Thoracic Surgeons (STS) risk scores. The anatomical compatibility for MitraClip invervention was assessed using the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) echocardiographic criteria. Results: Of 236 pts included in the study during 3 yrs, the cause of MR was FMR in 104 pts (44.1%), DMR in 84 (35.6%), and other causes (mainly endocarditis and rheumatic disease) in 48 (20.3%). Age and gender distribution were similar in pts with FMR (age 71±14 years, 62.5% male) and DMR (age 73±14 years, 66.7% male) and severe NYHA III/IV heart failure symptoms justifying intervention were evident in 73.1% and 60.7% of pts, respectively (P=0.10). Using multiple risk scores, the estimated surgical risk (mortality and major morbidity) for mitral valve repair or replacement (with or without bypass surgery) was consistently much higher in pts with FMR than DMR. Valve anatomy was suitable for MitraClip intervention in 87 pts (83.7%) with FMR versus only 38 pts (45.2%) with DMR (P&lt;0.001). Assuming the most common type of surgery was valve repair for DMR and annuloplasty + bypass surgery for FMR, and using an STS estimated mortality greater than 10% to define high surgical risk, only 6 pts with DMR (7.1%) had a clinical indication for intervention, high surgical risk, and valve anatomy suitable for MitraClip intervention, versus 21 pts (20.2%) with FMR (P&lt;0.001). Using an STS estimated mortality and morbidity greater than 20% to define high surgical risk, these proportions were 20 pts (23.8%) for DMR and 60 pts (57.7%) for FMR (P&lt;0.001). Conclusion: Higher surgical risk and better anatomical compatibility justify the greater use of MitraClip intervention in patients with FMR than in patients with DMR.
Loss of MGMT expression as a pre-neoplastic event favoring the emergence of MSI colorectal cancers
Authors: M. Svrcek, O. Buhard, S. Dumont, C. Colas, F. Coulet, J. Cosnes, E. Tiret, J. Fléjou, A. Duval
Journal: Journal of Clinical Oncology (2008)

4118 Background: O6-methylguanine-DNA methyltransferase (MGMT) is a repair enzyme whose depletion in vitro has been shown to favor the selection of mismatch repair (MMR) deficient clones. Inactivation of the MMR system lead cells to become malignant through the microsatellite instability (MSI) pathway. We hypothesized that MGMT depletion might constitute an early biomarker of MSI colorectal cancers (MSI CRCs). Since it may be a consequence of chronic inflammation, we therefore quantified the expression of MGMT in the tumor and normal appearing mucosa of patients suffering from inflammatory bowel diseases (IBD) or from the general population (non-IBD) and harboring a MSI or non-MSI (MSS) CRCs. Methods: We have investigated MGMT expression by immunohistochemistry in 82 non-IBD-CRCs (33 MSI, 49 MSS) and 54 IBD-CRCs (13 MSI, 41 MSS). MGMT expression was quantified in tumor, adjacent or distant mucosa, and also in the colon mucosa of non-IBD (n = 20) and IBD (n = 45) control cases with no evidence of cancer. Results: We observed a significant lack of MGMT expression in all tissues of non-IBD patients with CRCs (distant, adjacent and tumor mucosa) when compared to the colon mucosa of non-IBD controls (PD= 0.03; PA= 0.0003; PT= 0.0008; Fisher’s exact test), as previously reported. When considering the MSI status of non-IBD-CRCs, significant lack of MGMT expression was observed: (i) in adjacent and tumor mucosa, compared to distant mucosa, only in patients with a MSI CRC (PA/D = 0.005 and PT/D = 0.004); (ii) in adjacent and tumor mucosa of MSI CRCs compared to adjacent and tumor mucosa of MSS CRCs (PA = 0.025 and PT = 0.007). Overall, lack of MGMT expression was more frequent in the non transformed tissues of IBD patients and controls when compared to non-IBD patients and controls (P < 0.05; always significant). In IBD patients, this event appeared to be more pronounced in the tumor mucosa of patients developing a MSI CRCs when compared to MSS CRCs (PT = 0.06). Conclusions: Lack of MGMT expression is a pre-neoplastic event favoring MSI-driven colorectal carcinogenesis. Its occurrence is frequently observed both in the general population and, expectedly, at a higher frequency in IBD patients. These findings indicate that it may be used as an early biomarker for the detection of MSI CRCs. No significant financial relationships to disclose.
A Contemporary View of Diagnostic Cardiac Catheterization and Percutaneous Coronary Intervention in the United States
Authors: Gregory J. Dehmer, Douglas Weaver, Matthew T. Roe, Sarah Milford-Beland, Susan Fitzgerald, Anthony Hermann, John Messenger, Issam Moussa, Kirk Garratt, John Rumsfeld, Ralph G. Brindis
Journal: Journal of the American College of Cardiology (2012)
Determinants of personal ultraviolet-radiation exposure doses on a sun holiday
Authors: B. Petersen, E. Thieden, P.A. Philipsen, J. Heydenreich, H.C. Wulf, A.R. Young
Journal: British Journal of Dermatology (2013)

Journal Article Determinants of personal ultraviolet‐radiation exposure doses on a sun holiday Get access B. Petersen, B. Petersen Department of Dermatological Research, University of Copenhagen, Bispebjerg Hospital, DK‐2400, Copenhagen, Denmark Bibi Petersen. E‐mail: petersenbibi@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar E. Thieden, E. Thieden Department of Dermatological Research, University of Copenhagen, Bispebjerg Hospital, DK‐2400, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar P.A. Philipsen, P.A. Philipsen Department of Dermatological Research, University of Copenhagen, Bispebjerg Hospital, DK‐2400, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar J. Heydenreich, J. Heydenreich Department of Dermatological Research, University of Copenhagen, Bispebjerg Hospital, DK‐2400, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar H.C. Wulf, H.C. Wulf Department of Dermatological Research, University of Copenhagen, Bispebjerg Hospital, DK‐2400, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar A.R. Young A.R. Young King's College London, St John's Institute of Dermatology, London, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 5, 1 May 2013, Pages 1073–1079, https://doi.org/10.1111/bjd.12211 Published: 01 May 2013 Article history Accepted: 02 January 2013 Published: 01 May 2013