tbuckley/cabot-search huggingface dataset:
Tumor-suppressive function of micro-RNA mir-196a in colorectal cancer
Authors: Carl Schimanski, Kirsten Frerichs, Ines Gockel, Daniel Drescher, Martin Berger, Theodor Junginger, Markus Moehler, Peter Galle
Journal: Cancer Research (2007)

2183  Background: MicroRNAs as mir-196a are small endogenous RNAs, playing important roles in posttranscriptional gene expression regulation. Interestingly, siRNA-microarray analyses previously detected mir-196a transcription in human cancer cells. In mice, HoxC8 mRNA was restricted by mir-196a and mir-196a was furthermore predicted to interact with HoxD8 and HoxA7 mRNAs. As Hox genes are master regulators of proliferation and differentiation during embryogenesis, we analyzed the mir-196a function in human colorectal cancer and the clinical relevance of its target gene expression.  Methods: Colorectal cancer cell lines SW480, SW620 and HT29 were transientely transfected with mir-196a. Regulation of HoxB8, HoxD8 and HoxA7 was analyzed on a trancriptional and translational level. Transfected cells were applied in diverse functional assays (proliferation, adhesion, cell cycle analysis, migration, apoptosis). HoxB8, D8 and A7 transcription was evaluated in 100 colorectal cancer samples by PCR and correlated with clinico-pathological parameters.  Results: Transfection of SW480 and SW620 resulted in a rapid down-regulation of HoxB8, HoxD8 and HoxA7 expression. However, in HT29 no regulation could be observed. Mir-196a did not impact on proliferation, cell cycle or apoptosis but did increase cellular adhesion and inhibited migration. Mir-196a target gene HoxA7 and HoxD8 did not impact on clinical or pathological parameters. However, HoxB8 transcription, which was observed in 50% of samples, positively correlated with locally advanced and destructive primary cancers as indicated by the T-status (P  Conclusion: HoxB8, HoxD8 and HoxA7 are restriction targets of mir-196a in human cellular systems. Mir-196a inhibits migration and enhances cellular adhesion in vitro. Moreover, HoxB8 enhances local progression of colorectal cancers in vivo. Both results implicate a tumor-suppressive function of mir-196a.
Computer-assisted, interactive fundus image processing for macular drusen quantitation
Authors: David S Shin, Noreen B Javornik, Jeffrey W Berger
Journal: Ophthalmology (1999)

PurposeTo design and validate a software package to quantitate the area subtended by drusen in color fundus photographs for the conduct of efficient, accurate clinical trials in age-related macular degeneration.DesignAlgorithm and software development. Comparisons with manual methodologies.ParticipantsEvaluation and testing on color fundus photographs from patient records and from eyes enrolled in the Choroidal Neovascularization Prevention Trial.MethodsFundus photographs of eyes with drusen were digitized. The green channel was selected for maximum contrast and preprocessed with filtering and shade correction to minimize noise, improve contrast, and correct for illumination and background inhomogeneities. Local thresholding and region-growing algorithms identified drusen. Multiple levels of supervision were incorporated to maximize robustness, accuracy, and validity. Validation studies compared computer-assisted with manual grading by an experienced grader. Intraclass correlation coefficients were calculated as a measure of the concordance between manual and computer-assisted fundus gradings.Main outcome measuresDrusen area and concordance with manual grading.ResultsAutomated supervised image analysis offers extreme robustness and accuracy. Most images were segmented with little or no supervision, with processing times on the order of 5 seconds. More complicated images required supervision and a total analysis time varying from 20 seconds to 5 minutes, with most of this time devoted to inspection and comparison. Interactive image processing affords arbitrarily close concordance with manual drusen identification, with calculated intraclass correlation coefficients of 0.92 and 0.93 for comparison of manual with automated, supervised grading by two observers.ConclusionsAutomated supervised fundus image analysis is an efficient, robust, valid technique for drusen quantitation from color fundus photographs. This approach should prove useful in the conduct of efficient accurate clinical trials for age-related macular degeneration.
Abstract 3457: A possible role for the Hedgehog pathway ligands Desert and Indian in rhabdomyosarcoma
Authors: Josep Roma, Anna Almazán-Moga, Pablo Velasco, Carla Molist, Vidal Isaac, Miguel F. Segura, Aroa Soriano, Jubierre Luz, Paris Laia, Reventós Jaume, José Sánchez de Toledo, Soledad Gallego
Journal: Cancer Research (2014)

Abstract Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children, is thought to derive from embryonic cells committed to developing into skeletal muscle and is divided into 2 major subtypes: embryonal and alveolar (eRMS and aRMS, respectively). Hedgehog pathway-belonging proteins are considered to be key regulators of development in pluricellular organisms, exerting crucial roles in processes such as tissue patterning, proliferation and differentiation. Likewise, Hedgehog (HH) signaling also plays important roles in adult organisms such as stem cell maintenance or tissue repair. The 3 Hedgehog ligands present in mammals are named Sonic (SHH), Indian (IHH) and Desert (DHH). Upon binding of a Hedgehog ligand to Patched, active SMO is detected in the membrane and prevents GLI proteosomal processing. GLI is then translocated to the nucleus where it binds to and regulates GLI-specific promoters. Despite the knowledge gathered to date, the mechanism that drives activation of the pathway in RMS is not well understood; the relative importance of the 3 HH ligands has not been elucidated and a possible role for Desert or Indian HH in the pathogenesis of RMS has not been studied. Previous works reported undetectable levels of SHH in RMS tumors and cell lines with Hedgehog pathway activation, suggesting a mechanism of GLI1-upregulation independent of autocrine SHH expression. Herein, we report extremely low levels of SHH expression in the majority of RMS patients (approximately 70%). Conversely, we report a prominent expression of Desert and Indian HH ligands - instead of SHH - in RMS, thereby supporting the possible existence of an autocrine ligand-dependent activation of the Hedgehog pathway in this neoplasia. Furthermore, the expression of DHH significantly correlates with GLI1 levels, pointing to a crucial role of this ligand for the activation of the pathway in RMS. Citation Format: Josep Roma, Anna Almazán-Moga, Pablo Velasco, Carla Molist, Vidal Isaac, Miguel F. Segura, Aroa Soriano, Jubierre Luz, Paris Laia, Reventós Jaume, José Sánchez de Toledo, Soledad Gallego. A possible role for the Hedgehog pathway ligands Desert and Indian in rhabdomyosarcoma. [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 3457. doi:10.1158/1538-7445.AM2014-3457
Biomedical applications of accelerator mass spectrometry: kinetics of oxaliplatin-DNA binding in genomic DNA and human cancer cells
Authors: Sang Soo Hah, Rhoda Sumbad
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3205 

Oxaliplatin is a relatively new platinum analogue that is currently used in chemotherapy of metastatic colorectal cancer. Oxaliplatin exerts its anti-tumor effects by covalent modification of DNA to form monoadducts, and intra- and interstrand diadducts, like other platinum-based anticancer drugs such as cisplatin and carboplatin. Very recently, we reported the use of accelerator mass spectrometry (AMS), an extremely sensitive detection method, to measure both in vitro and cell-based kinetics of carboplatin-DNA monoadduct formation. We report an application of our approach to measurement of both the kinetics of [14C]oxaliplatin-DNA adduct formation with genomic DNA and drug uptake and DNA binding in 833K human testicular cancer cells, T24 human bladder cancer cells and MDA-MB-231 multi-drug resistant human breast cancer cells. A strength of this approach is that because radiocarbon is located in the carrier group, not only the total amount of oxaliplatin-DNA adducts can be measured, but a series of adducts can also be discriminated following DNA digestion and HPLC separation. The in vitro binding study of [14C]oxaliplatin to salmon sperm DNA, and digestion of the resulting platinated DNA followed by HPLC-AMS measurement, allowed for straightforward kinetic calculations that revealed the mechanism of action for oxaliplatin, and for differential oxaliplatin-DNA adduct formation as a function of time. In addition, 833K cells, T24 cells and MDA-MB-231 cells were incubated with a sub-pharmacological dose of [14C]oxaliplatin, resulting in the both drug uptake and oxaliplatin-DNA adduct quantitation. Interestingly, HPLC-AMS data of the digested DNA resulting from the incubation of [14C]oxaliplatin with T24 cells for 24 h shows a similar compositional pattern, but a significantly different mass distribution of oxaliplatin-DNA adducts, compared with that from the in vitro experiments. Of importance, the lowest concentration of radiocarbon measured was approximately 1 amol/1 μg of DNA. This sensitivity may allow the method to be useful for clinical applications. Work was performed at the Research Resource for Biomedical AMS, operated at UC LLNL under the auspices of the U.S. DOE contract #W-7405-ENG-48 and partially supported by NIH/NCRR, Biomedical Technology Program grant #P41 RR13461 and DOE/LDRD grant 06-LW-023.
Failed Degradation of JunB Contributes to Overproduction of Type I Collagen and Development of Dermal Fibrosis in Patients With Systemic Sclerosis
Authors: Markella Ponticos, Ioannis Papaioannou, Shiwen Xu, Alan M. Holmes, Korsa Khan, Christopher P. Denton, George Bou‐Gharios, David J. Abraham
Journal: Arthritis & Rheumatology (2014)

The excessive deposition of extracellular matrix, including type I collagen, is a key aspect in the pathogenesis of connective tissue diseases such as systemic sclerosis (SSc; scleroderma). To further our understanding of the mechanisms governing the dysregulation of type I collagen production in SSc, we investigated the role of the activator protein 1 (AP-1) family of transcription factors in regulating COL1A2 transcription.The expression and nuclear localization of AP-1 family members (c-Jun, JunB, JunD, Fra-1, Fra-2, and c-Fos) were examined by immunohistochemistry and Western blotting in dermal biopsy specimens and explanted skin fibroblasts from patients with diffuse cutaneous SSc and healthy controls. Gene activation was determined by assessing the interaction of transcription factors with the COL1A2 enhancer using transient transfection of reporter gene constructs, electrophoretic mobility shift assays, chromatin immunoprecipitation analysis, and RNA interference involving knockdown of individual AP-1 family members. Inhibition of fibroblast mammalian target of rapamycin (mTOR), Akt, and glycogen synthase kinase 3β (GSK-3β) signaling pathways was achieved using small-molecule pharmacologic inhibitors.Binding of JunB to the COL1A2 enhancer was observed, with its coalescence directed by activation of gene transcription through the proximal promoter. Knockdown of JunB reduced enhancer activation and COL1A2 expression in response to transforming growth factor β. In SSc dermal fibroblasts, increased mTOR/Akt signaling was associated with inactivation of GSK-3β, leading to blockade of JunB degradation and, thus, constitutively high expression of JunB.In patients with SSc, the accumulation of JunB resulting from altered mTOR/Akt signaling and a failure of proteolytic degradation underpins the aberrant overexpression of type I collagen. These findings identify JunB as a potential target for antifibrotic therapy in SSc.
Abstract 15298: A New Scoring System for the Prediction of Paroxysmal Atrial Fibrillation Progression and Relationship with Clinical Outcomes
Authors: Hyung Wook Park, Ki Hong Lee, Nam Sik Yoon, Jeong Gwan Cho, Sung Soo Kim, Cheol Hwan Kim, Kyung Hwan Kim, Seung Jin Jun, Woo Jin Kim, Min Chul Kim, Kyung Hoon Cho, Kyoung Jin Lee, Hae Chang Jeong, Jae Yeong Cho, Keun-Ho Park, Doo Sun Sim, Hyun Joo Yoon, Kye Hun Kim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Jong Chun Park, Myung Ho Jeong
Journal: Circulation (2014)

Background: The progression of paroxysmal atrial fibrillation (AF) to persistent, long lasting persistent AF is often associated with poor clinical outcomes. Although some factors were known to be useful, their accuracy and clinical relationship are not good enough to predict the progression. Hypothesis: We aimed to construct a new predictive scoring system for the progression of paroxysmal AF. Also, we aimed to evaluate the relationship of a new predicting system with clinical outcomes. Methods: We analyzed 2,047 patients (61.2±13.2 years old, 1158 males) who were newly diagnosed as AF from January 2006 to January 2013. Progression of AF and clinical outcomes were analyzed after at least one-year follow-up. Clinical outcomes were defined as the composite of death, hospitalization due to heart failure, and new onset stroke. Independent predictors of AF progression were analyzed and incorporated into a new predictive scoring system. Its predictive accuracy was compared with CHADS 2 , CHA 2 DS 2 -VASc, and HATCH scoring system. Results: Paroxysmal AF was diagnosed in 449 (21.6%) patients. Among them, 78 (17.4%) patients progressed to persistent AF. Multivariate analysis showed congestive heart failure (LVEF &lt;45%), hypertension, older age (≥65 years old), chronic renal disease, previous history of stroke, COPD, left atrial enlargement (≥43mm), high NT-pro BNP serum levels (≥1,000 pg/mL) were independently associated with the progression. A new scoring system was calculated with the sum of 1 point at each independent risk factor. It showed better predictive accuracy for AF progression (area under curve (AUC): 0.754, 95% confidence interval [CI] 0.69-0.83, p&lt;0.001) than CHADS 2 (AUC 0.643; 95% CI 0.58-0.71), CHA 2 DS 2 -VASc (AUC 0.647; 95% CI 0.58-0.71), and HATCH score (AUC 0.675; 95% CI 0.61-0.74). Also, it showed better predictive accuracy for the composite of clinical outcomes (AUC 0.764, 95% CI 0.68-0.83, p&lt;0.001) with linear correlation (linear p&lt;0.001) than the other scoring systems. More than 60% of patients with paroxysmal AF progressed into sustained AF if the score by a new system was more than 3. Conclusions: A new scoring system may help to the prediction of AF progression and prognosis for clinical outcomes in patients with paroxysmal AF.
A European laboratory network for sequence-based typing of methicillin-resistant Staphylococcus aureus (MRSA) as a communication platform between human and veterinary medicine – an update on SeqNet.org
Authors: A W Friedrich, W Witte, H de Lencastre, W Hryniewicz, J Scheres, H Westh, Collective SeqNet.org participants
Journal: Eurosurveillance (2008)

Binary file ES_Abstracts_Final_ECDC.txt matches
Unrest in Baltimore
Authors: Leana S. Wen, Joshua M. Sharfstein
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
Genetically engineered Bifidobacterium longum expressing cytosine deaminase for tumor-targeting enzyme-prodrug therapy
Authors: Takayuki Sasaki, Minoru Fujimori, Yoshinori Hamaji, Yoshihisa Hama, Ken-Ichi Ito, Jun Amano, Shun’ichiro Taniguchi
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4023 

Cancer gene therapy approaches to solid tumor treatment have been limited by the delivering ability to achieve specific high-level expression of the gene product within tumor cells or the tissues following the systemic vector administration. Since hypoxia is characteristic of most solid tumors, gene therapies targeting to hypoxic tumor cells having been investigated. We previously reported that a strain of domestic nonpathogenic and anaerobic bacteria, Bifidobacterium longum ( B. longum ), selectively localized and proliferated within solid tumors after the systemic administration. Here, we propose a novel approach to cancer therapy in which anaerobic bacteria of the genus B. longum are used to achieve tumor-specific delivery of a desired agent and enzyme-prodrug therapy. We constructed an expression vector, pBLES100-S-eCD, of E. coli cytosine deaminase gene ( eCD ), transfecting it into B. longum by electroporation. We confirmed that the transformed B. longum ( B. longum /S-eCD) localized and grew specifically in solid tumors and that the cytosine deaminase (CD) was produced in the B. longum/ S-eCD detected in the tumors by Gram’s stain and immunostaining for CD. Such cytosine deaminase (CD) production in hypoxic tumors resulted in the tumor site-specific conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). Furthermore, we observed growth suppression of autochthonous mammary tumors chemically-induced in rats by both direct and intravenous administration of B. longum /S-eCD. This method was thus confirmed to be effective irrespective of the systemic administration or the intra-tumoral injection. To further estimate the safety of the non-pathogenic B. longum /S-eCD, the immunogenicity was examined through Active Systemic Anaphylaxis (ASA) reaction and passive cutaneous anaphylaxis (PCA) reaction in guinea pigs. In ASA reaction, no anaphylaxis symptom was observed in any immunized guinea-pigs injected with B.longum /S-eCD. In PCA reaction, no anti- Blongum /S-eCD antibody was detected, either. These results surprised us and also made us convinced that Blongum /S-eCD was safely used for a tumor-specific delivery system. The clinical effectiveness of 5-FU in conventional therapy has been limited by its high degree of the systemic toxicity, particularly toward the bone marrow. However, the enzyme-prodrug therapeutic strategy using B. longum /S-eCD and 5-FC shown here appeared to be safer and more effective, because of the specific generation of 5-FU at the tumor site but not at other normal tissues, than conventional chemotherapies with 5-FU. Taken these findings together, we believe that obligate anaerobic bacteria, such as the genus B. longum , are safe and attractive tools to specifically produce desired anti-tumor agents in enzyme-prodrug therapy of solid tumors.
Thrombophilic dysfibrinogen Tokyo V with the amino acid substitution of γ Ala327Thr: formation of fragile but fibrinolysis-resistant fibrin clots and its relevance to arterial thromboembolism
Authors: Akiei Hamano, Jun Mimuro, Motonori Aoshima, Takeyoshi Itoh, Noboru Kitamura, Susumu Nishinarita, Katsuhiro Takano, Akira Ishiwata, Yuji Kashiwakura, Kazuki Niwa, Tomoko Ono, Seiji Madoiwa, Teruko Sugo, Michio Matsuda, Yoichi Sakata
Journal: Blood (2004)
Cutaneous T‐cell lymphoma: 2014 Update on diagnosis, risk‐stratification, and management
Authors: Ryan A. Wilcox
Journal: American Journal of Hematology (2014)

Disease overview : Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Diagnosis : The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk‐adapted therapy : TNMB (tumor, node, metastasis, and blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral or blood involvement are generally approached with biologic‐response modifiers or histone deacetylase inhibitors prior to escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy (e.g., CHOP) may be employed for those patients with extensive visceral involvement requiring rapid disease control. In highly selected patients, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol. 89:837–851, 2014. © 2014 Wiley Periodicals, Inc.
A patient who changed my practice: Northern Ireland weather
Authors: K. A Choudhari
Journal: BMJ (2003)

With my appointment as a neurosurgeon in Belfast, I realised that most patients desired some personal and informal interaction. They also wanted to know more about me. Being rather reserved, I found it difficult to engage in long conversations. Also, not being a native of Northern Ireland, there were few subjects in common to talk about. After pleasantries and discussion of the medical condition, I was usually at a loss to extend the conversation further. I was aware of the sectarian troubles, but patients avoided such sensitive topics. Soon, I discovered that one topic was popular, uncontentious, and universally discussed by Protestant and Catholic alike—the weather. Good weather was an exception rather than the rule. None the …
The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells
Authors: H Stein, DY Mason, J Gerdes, N O'Connor, J Wainscoat, G Pallesen, K Gatter, B Falini, G Delsol, H Lemke, R Schwarting, K Lennert
Journal: Blood (1985)
An Attempt to Demonstrate a Y-Linked Histocompatibility Gene in the House Mouse&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Seldon E. Bernstein, Abigail A. Silvers, Willys K. Silvers
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article An Attempt to Demonstrate a Y-Linked Histocompatibility Gene in the House Mouse Get access Seldon E. Bernstein, Seldon E. Bernstein Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Abigail A. Silvers, Abigail A. Silvers Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Willys K. Silvers Willys K. Silvers Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 3, March 1958, Pages 577–580, https://doi.org/10.1093/jnci/20.3.577 Published: 01 March 1958 Article history Received: 16 September 1957 Published: 01 March 1958
Guidelines for clinical intracardiac electrophysiological and catheter ablation procedures
Authors: Douglas P. Zipes, John P. Dimarco, Paul C. Gillette, Warren M. Jackman, Robert J. Myerburg, Shahbudin H. Rahimtoola, James L. Ritchie, Melvin D. Cheitlin, Arthur Garson, Raymond J. Gibbons, Richard P. Lewis, Robert A. O'Rourke, Thomas J. Ryan, Robert C. Schlant
Journal: Journal of the American College of Cardiology (1995)