tbuckley/cabot-search huggingface dataset:
Diphenyl Difluoroketone: A Curcumin Derivative with Potent <i>In vivo</i> Anticancer Activity
Authors: Dharmalingam Subramaniam, Randal May, Sripathi M. Sureban, Katherine B. Lee, Robert George, Periannan Kuppusamy, Rama P. Ramanujam, Kalman Hideg, Brian K. Dieckgraefe, Courtney W. Houchen, Shrikant Anant
Journal: Cancer Research (2008)

Abstract Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was reported to inhibit proliferation of a variety of cancer cells in vitro. However, the efficacy and in vivo mechanism of action of EF24 in gastrointestinal cancer cells have not been investigated. Here, we assessed the in vivo therapeutic effects of EF24 on colon cancer cells. Using hexosaminidase assay, we determined that EF24 inhibits proliferation of HCT-116 and HT-29 colon and AGS gastric adenocarcinoma cells but not of mouse embryo fibroblasts. Furthermore, the cancer cells showed increased levels of activated caspase-3 and increased Bax to Bcl-2 and Bax to Bcl-xL ratios, suggesting that the cells were undergoing apoptosis. At the same time, cell cycle analysis showed that there was an increased number of cells in the G2-M phase. To determine the effects of EF24 in vivo, HCT-116 colon cancer xenografts were established in nude mice and EF24 was given i.p. EF24 significantly suppressed the growth of colon cancer tumor xenografts. Immunostaining for CD31 showed that there was a lower number of microvessels in the EF24-treated animals coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA and protein expression. Western blot analyses also showed decreased AKT and extracellular signal-regulated kinase activation in the tumors. Taken together, these data suggest that the novel curcumin-related compound EF24 is a potent antitumor agent that induces caspase-mediated apoptosis during mitosis and has significant therapeutic potential for gastrointestinal cancers. [Cancer Res 2008;68(6):1962–9]
Diagnostic role of micro-MGIT culture of BAL samples in sputum smear-negative pulmonary tuberculosis
Authors: Jagdish Rawat, Girish Sindhwani, Debasis Biswas
Journal: European Respiratory Journal (2012)

Introduction: In view of the diagnostic difficulties associated with sputum- negative pulmonary TB (PTB), we aimed at exploring if bronchoalveolar lavage (BAL) samples can be subjected to smear- microscopy and rapid mycobacterial culture (by Mycobacterial Growth Indicator Tube method) to achieve improved diagnosis of this condition.  Methods: Patients presenting with clinico-radiological features suggestive of pulmonary tuberculosis and whose sputum smears were negative for acid- fast bacilli (AFB) or who could not expectorate sputum were prospectively enrolled in this study. BAL samples collected from them were subjected to smear- microscopy for AFB and micro-MGIT culture. BAL samples were also inoculated on Lowenstein- Jensen (LJ) slants.  Results: A total of 105 patients (74 males) were recruited in the study, with a mean (±SD) age of 51 (± 15) years. The diagnosis of PTB was made in 52 patients on the basis of clinico- radiological presentation, with or without microbiological confirmation. Thirty- four patients (65.4 %) had microbiologically confirmed PTB. Of them, AFB was detected in 12 BAL samples, while culture- positivity was noted in 24 and 27 patients by the LJ and MGIT methods respectively. Inter- test agreement between the LJ and MGIT methods was found to be significant (κ= 0.655; p=   Conclusion: Examination of BAL samples by smear- microscopy and micro-MGIT culture can, therefore, provide a rapid and definitive diagnosis of PTB in sputum- negative patients.  Keyword: MGIT, micro-MGIT, smear negative pulmonary tuberculosis, bronchoscopy.
Sources of Regional Variation in Medicare Part D Drug Spending
Authors: Julie M. Donohue, Nancy E. Morden, Walid F. Gellad, Julie P. Bynum, Weiping Zhou, Joseph T. Hanlon, Jonathan Skinner
Journal: New England Journal of Medicine (2012)

Sources of regional variation in spending for prescription drugs under Medicare Part D are poorly understood, and such variation may reflect differences in health status, use of effective treatments, or selection of branded drugs over lower-cost generics.
SNO-ing at the Nociceptive Synapse?
Authors: Irmgard Tegeder, Reynir Scheving, Ilka Wittig, Gerd Geisslinger
Journal: Pharmacological Reviews (2011)

Nitric oxide is generally considered a pronociceptive retrograde transmitter that, by activation of soluble guanylyl cyclase-mediated cGMP production and activation of cGMP-dependent protein kinase, drives nociceptive hypersensitivity. The duality of its functions, however, is increasingly recognized. This review summarizes nitric-oxide–mediated direct S-nitrosylation of target proteins that may modify nociceptive signaling, including glutamate receptors and G-protein-coupled receptors, transient receptor potential channels, voltage-gated channels, proinflammatory enzymes, transcription factors, and redoxins. S-Nitrosylation events require close proximity of nitric oxide production and target proteins and a permissive redox state in the vicinity. Despite the diversity of potential targets and effects, three major schemes arise that may affect nociceptive signaling: 1) S-Nitrosylation-mediated changes of ion channel gating properties, 2) modulation of membrane fusion and fission, and thereby receptor and channel membrane insertion, and 3) modulation of ubiquitination, and thereby protein degradation or transcriptional activity. In addition, S-Nitrosylation may alter the production of nitric oxide itself.
Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907)
Authors: K.J. Ruddy, B.N. Pitcher, L.E. Archer, H.J. Cohen, E.P. Winer, C.A. Hudis, H.B. Muss, A.H. Partridge
Journal: Annals of Oncology (2012)
Clinical Characteristics Affect the Impact of an Uninformative DNA Test Result: The Course of Worry and Distress Experienced by Women Who Apply for Genetic Testing for Breast Cancer
Authors: Sandra van Dijk, Daniëlle R.M. Timmermans, Hanne Meijers-Heijboer, Aad Tibben, Christi J. van Asperen, Wilma Otten
Journal: Journal of Clinical Oncology (2006)

Purpose DNA mutation testing for breast cancer usually yields an uninformative result, which is a negative result in the absence of a known BRCA mutation within the family. However, few data are available on the psychological impact of this result. Moreover, the clinical heterogeneity within this group has not yet been considered. This study provides prospective data about the course of cancer-specific worry and distress for different groups of test applicants. Patients and Methods All DNA test applicants (n = 238) completed three questionnaires: before and 1 and 7 months after disclosure of a DNA mutation test. With repeated-measures analysis of variance, differences were assessed between BRCA1/2-positive women (n = 42), BRCA1/2–true-negative women (n = 43), and women with an uninformative test result (n = 153). Results On the group level, women with an uninformative result seemed to be reassured after disclosure (P &lt; .001), but to a lesser extent than those women who received a true-negative result. However, not all women with an uninformative result reacted similarly: higher levels of worry and distress could be explained by relatively straightforward clinical variables, namely a personal history of cancer (P ≤ .001) and a higher pedigree-based risk (P ≤ .005). Furthermore, these clinical variables determined whether these women were either comparable to women who received a true-negative result or to BRCA mutation carriers. Conclusion Women with an uninformative result form a heterogeneous group of test applicants. The subpopulation of those with both a personal history of cancer and a relatively high pedigree-based risk expressed the highest levels of worry 7 months after DNA testing.
Acute subclavian steal syndrome following blunt thoracic trauma
Authors: A. Blesovsky, V. Colanceski, J. Ferguson, W. Urquhart
Journal: Thorax (1972)

A rare case of acute subclavian steal syndrome following blunt thoracic trauma is described. By aortography, obstruction of the origin of the left subclavian artery was found and the reversed flow through the vertebral artery was demonstrated. This injury was successfully treated by an aortosubclavian bypass Dacron prosthesis using a left posterolateral thoracotomy approach.
Hereditary hemorrhagic telangiectasia: an update on transforming growth factor ? signaling in vasculogenesis and angiogenesis
Authors: S VANDENDRIESCHE, C MUMMERY, C WESTERMANN
Journal: Cardiovascular Research (2003)

Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder in humans which has been mapped to two genes, endoglin and activin receptor-like kinase-1 (ALK-1) both of which mediate signaling by transforming growth factor β ligands in vascular endothelial cells. Animal models have shown that these receptors are not only important for maintaining vascular integrity but also for angiogenesis both during embryonic development and during tumor growth. Here, we review the current status of reported mutations in the context of the clinical manifestations and the effects on the vessel wall both in patients and in animal models of the disease.
The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency
Authors: Venetia Bigley, Muzlifah Haniffa, Sergei Doulatov, Xiao-Nong Wang, Rachel Dickinson, Naomi McGovern, Laura Jardine, Sarah Pagan, Ian Dimmick, Ignatius Chua, Jonathan Wallis, Jim Lordan, Cliff Morgan, Dinakantha S. Kumararatne, Rainer Doffinger, Mirjam van der Burg, Jacques van Dongen, Andrew Cant, John E. Dick, Sophie Hambleton, Matthew Collin
Journal: The Journal of Experimental Medicine (2011)

Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage− compartment, with virtually no CD123+ or CD11c+ dendritic cells (DCs) and very few CD14+ or CD16+ monocytes. The only remaining HLA-DR+ lineage− cells were circulating CD34+ progenitor cells. Dermal CD14+ and CD1a+ DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.
Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease
Authors: S E Crowe, G K Luthra, M H Perdue
Journal: Gut (1997)

Background —Mast cells have been shown to regulate intestinal ion transport in animal models and normal human colon but their physiological role in human intestinal inflammatory disorders is unknown. Aims —To examine mast cell regulation of ion transport in inflammatory bowel disease (IBD). Subjects and methods —Small and large intestine was obtained from patients with and without IBD undergoing surgical resection. Short circuit current ( I sc) responses to rabbit antihuman IgE, histamine, and electrical stimulation were measured in Ussing chambers. Specimens were also examined for mast cell numbers and degree of inflammation. Results — I sc responses to anti-IgE and histamine were smaller in magnitude in IBD compared with non-IBD tissues. In all tissues, anti-IgE I sc responses were reduced by about 80% in chloride free buffer. The histamine H 1 receptor antagonist, pyrilamine, decreased anti-IgE responses in non-IBD tissues. Greater inhibition with pyrilamine was seen in IBD small intestine but its effect was less in IBD colon. Histamine pretreatment of non-IBD control tissues reduced anti-IgE responses to levels seen in IBD colon but had no effect in small intestine. Mast cell numbers were greater in IBD compared with non-IBD small intestine while no differences were observed between the colonic groups. I sc responses to anti-IgE were not correlated with the degree of mucosal inflammation. Conclusions —This study provides further evidence that mast cells are capable of mediating alterations of ion transport in human gut but that this regulatory role may be altered in IBD. The data suggest that prior activation of mast cells with release of histamine may account for the reduced secretory response to anti-IgE observed in IBD colonic tissues.
Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study
Authors: Fred R. Hirsch, Marileila Varella-Garcia, Jason McCoy, Howard West, Ana Carolina Xavier, Paul Gumerlock, Paul A. Bunn, Wilbur A. Franklin, John Crowley, David R. Gandara
Journal: Journal of Clinical Oncology (2005)

Purpose Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established. Patients and Methods EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy). Results In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P = .087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients; P &gt; .10). Conclusion Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors.
Glatiramer acetate (Copaxone) therapy induces CD8+ T cell responses in patients with multiple sclerosis
Authors: Nitin J. Karandikar, Michael P. Crawford, Xiao Yan, Robert B. Ratts, Jason M. Brenchley, David R. Ambrozak, Amy E. Lovett-Racke, Elliot M. Frohman, Peter Stastny, Daniel C. Douek, Richard A. Koup, Michael K. Racke
Journal: Journal of Clinical Investigation (2002)

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine that is used therapeutically in patients with multiple sclerosis (MS). To investigate the mechanism of the drug's immunomodulatory effect, we used immunophenotypic approaches to characterize the precise nature of GA-induced T cell responses. We demonstrate here that healthy individuals and untreated MS patients exhibit prominent T cell proliferative responses to GA. However, these responses are different in distinct subsets of T cells. Whereas GA-induced CD4+ T cell responses are comparable in healthy individuals and MS patients, CD8+ T cell responses are significantly lower in untreated MS patients. Treatment with GA results in upregulation of these CD8+ responses with restoration to levels observed in healthy individuals. Both CD4+ and CD8+ GA-specific responses are HLA-restricted. GA therapy also induces a change in the cytokine profile of GA-specific CD4+ and CD8+ T cells. This study provides the first direct immunophenotypic evidence, to our knowledge, of GA-specific CD8+ T cell responses and their upregulation during the course of therapy, which may suggest a role for these responses in the immunomodulatory effects of the drug.
Combined Gene Expression and Genomic Profiling Define Two Intrinsic Molecular Subtypes of Urothelial Carcinoma and Gene Signatures for Molecular Grading and Outcome
Authors: David Lindgren, Attila Frigyesi, Sigurdur Gudjonsson, Gottfrid Sjödahl, Christer Hallden, Gunilla Chebil, Srinivas Veerla, Tobias Ryden, Wiking Månsson, Fredrik Liedberg, Mattias Höglund
Journal: Cancer Research (2010)

Abstract In the present investigation, we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes, we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1 in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data show that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathologic data, it was possible to distinguish two molecular subtypes of Ta and T1 tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low-grade (G1/G2) and high-grade (G3) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathologic grading. We also present a gene expression signature with independent prognostic effect on metastasis and disease-specific survival. We conclude that the combination of molecular and histopathologic classification systems might provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type. Cancer Res; 70(9); 3463–72. ©2010 AACR.
A tiling resolution DNA microarray with complete coverage of the human genome
Authors: Adrian S Ishkanian, Chad A Malloff, Spencer K Watson, Ronald J deLeeuw, Bryan Chi, Bradley P Coe, Antoine Snijders, Donna G Albertson, Daniel Pinkel, Marco A Marra, Victor Ling, Calum MacAulay, Wan L Lam
Journal: Nature Genetics (2004)
Expression of Cdx2 and Hepatocyte Antigen in Gastric Carcinoma: Correlation with Histologic Type and Implications for Prognosis
Authors: Zhaoqing Fan, Jiyou Li, Bin Dong, Xinfu Huang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: This study was designed to (a) analyze the correlation between the expression of Cdx2 and Hep and the clinicopathologic features of patients with gastric carcinoma, and (b) determine the value of combined analysis of Cdx2 and Hep expression in distinguishing histologic types and prognoses of gastric carcinomas. Experimental Design: The expression of Cdx2 and Hep were studied using immunohistochemistry of paraffin-embedded tumor specimens from 109 patients who underwent D2 resection for gastric adenocarcinoma from 1995 to 1998. Results: Nuclear Cdx2 and Hep expression was detected in 36.7% (40 of 109) and 54.1% (59 of 109) of gastric carcinoma cases, respectively. Expression of Cdx2 and Hep was significantly higher in intestinal-type carcinomas than in diffuse-type carcinomas (P = 0.027 and P = 0.037, respectively). There was a clear negative correlation between Cdx2 expression and lymph node metastasis (P = 0.029), as well as between Hep expression and depth of wall invasion (P = 0.011). The patients with Cdx2-positive or Hep-positive expression shows higher survival rate than those with Cdx2-negative or Hep-negative expression (P = 0.0008 and P = 0.003, respectively). Multivariate analysis revealed that the expression of Cdx2 and Hep were independent prognostic indicators of gastric carcinoma. The combination of Cdx2 and Hep expression was significantly lower in diffuse-type carcinoma than in intestinal or mixed-type carcinoma. Multivariate analysis revealed that Cdx2 and Hep expression was an independent prognostic indicator of gastric carcinoma (P &amp;lt; 0.001). Conclusions: These data suggest that combined analysis of Cdx2 and Hep has significant value in distinguishing histologic types and in predicting the prognosis of gastric carcinoma.
Swimming in the Sea of Galilee
Authors: Ora Hirsch Pescovitz
Journal: JAMA (2013)

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