tbuckley/cabot-search huggingface dataset:
Abstract 3591: 15-Deoxy-Δ12,14-prostaglandin J2-induced epithelial-to-mesenchymal transition in human breast cancer cells promotes fibroblast activation
Authors: Do-Hee Kim, Jeehye Choi, Jin-Young Suh, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2014)

Abstract In inflammation-associated carcinogenesis, cyclooxygenase-2 (COX-2) is markedly overexpressed, resulting in accumulation of various prostaglandins. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and prostahlandin E2 (PGE2) are the predominant COX-2-derived prostaglandins (PGs) with oncogenic potential. In the present study, we examined the effects of these to PGs on epithelial-to-mesenchymal transition (EMT), a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. 15d-PGJ2 induced EMT to a greater than PGE2 in human breast cancer (MCF-7) cells. Snail and ZEB1 are known to bind to the E-boxes present in the E-cadherin promoter, thereby repressing E-cadherin transcription. Treatment of MCF-7 cells with 30 μM of 15d-PGJ2 increased the expression of Snail and ZEB1, followed by the down-regulation of E-cadherin. Nuclear extract from 15d-PGJ2-treated MCF-7 cells showed the binding of Snail and ZEB1 to E-box sequences in the E-cadherin promoter. In addition, among various cytokines/chemokines examined, the mRNA level of interleukin-8 (CXCL8) was highly elevated in 15d-PGJ2-stimulated MCF-7 cells. 15d-PGJ2-induced up-regulation of CXCL8 expression was abrogated by the introduction of Snail short interfering RNA. These findings suggest that CXCL8 may function as a positive regulator of EMT in 15d-PGJ2-treated MCF-7 cells. Moreover, the addition of conditioned medium of MCF-7 cells undergoing EMT activates normal fibroblast cells to cancer-associated fibroblasts (CAFs). Co-culture of normal fibroblasts with 15d-PGJ2-treaed-MCF-7 cells also induced the expression of α-SMA and FAPα, representative markers of CAFs. As a corresponding receptor of CXCL8, CXCR2 was overexpressed in activated fibroblasts co-cultured with 15d-PGJ2-treated MCF-7 cells. Unlike 15d-PGJ2, its non-electrophilic analogue 9,10-dihydro-15d-PGJ2 failed to induce EMT, suggesting that the α,β-unsaturated carbonyl group located in the cyclopentenone ring of 15d-PGJ2 is essential for EMT induction. Notably, activation of Rho kinase through direct binding of ArhGEF5, a guanine nucleotide exchange factor, with 15d-PGJ2 seems to contribute to the EMT induction. Taken together, above findings suggest that 15d-PGJ2 induces EMT through up-regulation of Snail expression and subsequent production of CXCL8 which may contribute to increased EMT of human breast cancer cells. Citation Format: Do-Hee Kim, Jeehye Choi, Jin-Young Suh, Hye-Kyung Na, Young-Joon Surh. 15-Deoxy-Δ12,14-prostaglandin J2-induced epithelial-to-mesenchymal transition in human breast cancer cells promotes fibroblast activation. [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 3591. doi:10.1158/1538-7445.AM2014-3591
American Board of Internal Medicine and Maintenance of Certification Standards
Authors: Richard J. Baron
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Gender Disparity and Mutation Burden in Metastatic Melanoma
Authors: Sameer Gupta, Mykyta Artomov, William Goggins, Mark Daly, Hensin Tsao
Journal: JNCI Journal of the National Cancer Institute (2015)

Gender differences in melanoma incidence and outcome have been consistently observed but remain biologically unexplained. We hypothesized that tumors are genetically distinct between men and women and analyzed the mutation spectra in 266 metastatic melanomas (102 women and 164 men) from The Cancer Genome Atlas (TCGA). We found a statistically significantly greater burden of missense mutations among men (male median 298 vs female median = 211.5; male-to-female ratio [M:F] = 1.85, 95% confidence interval [CI] = 1.44 to 2.39). We validated these initial findings using available data from a separate melanoma exome cohort (n = 95) and found a similar increase in missense mutations among men (male median 393 vs female median 259; M:F = 1.59, 95% CI = 1.12 to 2.27). In addition, we found improved survival with increasing log-transformed missense mutation count (univariate hazard ratio = 0.82, 95% CI = 0.69 to 0.98) for TCGA samples. Our analyses demonstrate for the first time a gender difference in mutation burden in cutaneous melanoma.
Exome capture and allinone sequencing to identify potential single nucleotide polymorphisms associated with spontaneous hepatitis C virus clearance
Authors: Huiying Rao, Guangqing Sun, Dong Jiang, Fusheng He, Jianghua Wang, Yu Xu, Heng-Hui Zhang, Xuemei Li, Ruifeng Yang, Yinghao Wang, Haiying Zhang, Jian Wang, Degui Sun, Yingrui Li, Ruyu Liu, Jun Wang, Lai Wei
Journal: Hepatology (2013)
Brief Report: Chikungunya Viral Arthritis in the United States: A Mimic of Seronegative Rheumatoid Arthritis
Authors: Jonathan J. Miner, Han Xian Aw Yeang, Julie M. Fox, Samantha Taffner, Olga N. Malkova, Stephen T. Oh, Alfred H. J. Kim, Michael S. Diamond, Deborah J. Lenschow, Wayne M. Yokoyama
Journal: Arthritis & Rheumatology (2015)

Objective Chikungunya virus (CHIKV) is an arthritogenic mosquito‐transmitted alphavirus that spread to the Caribbean in 2013 and to the US in 2014. CHIKV‐infected patients develop inflammatory arthritis that can persist for months or years, but little is known about the rheumatologic and immunologic features of CHIKV‐related arthritis in humans, particularly as compared to rheumatoid arthritis (RA). The purpose of this study was to describe these features in a group of 10 American travelers who were nearly simultaneously infected while visiting Haiti in June 2014. Methods Patient history was obtained and physical examination and laboratory tests were performed. All patients with CHIKV‐related arthritis had detectable levels of anti‐CHIKV IgG. Using cytometry by time‐of‐flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV‐infected patients, healthy controls, and patients with untreated, active RA. Results Among 10 CHIKV‐infected individuals, 8 developed persistent symmetric polyarthritis that met the American College of Rheumatology/European League Against Rheumatism 2010 criteria for (seronegative) RA. CyTOF analysis revealed that RA and CHIKV‐infected patients had greater percentages of activated and effector CD4+ and CD8+ T cells than healthy controls. Conclusion In addition to similar clinical features, patients with CHIKV infection and patients with RA develop very similar peripheral T cell phenotypes. These overlapping clinical and immunologic features highlight a need for rheumatologists to consider CHIKV infection when evaluating patients with new, symmetric polyarthritis.
Abstract 3605: The inhibitor of NF-ĸB kinase, IKKβ, regulates the stability of GLI1 transcription factor
Authors: Nitin K. Agarwal, Kranthi Kunkalla, Francisco Vega
Journal: Cancer Research (2014)

Abstract Lymphoma microenvironment has a crucial role in lymphoma initiation, progression and drug resistance. Fibroblastic reticular cells (FRCs) participate dynamically in the cytokine microenvironment of the lymph node paracortex as well as the regulation of cell trafficking and access of T-cells into the paracortex. The FRC niche also participates in the cytokine microenvironment of lymphomas providing homing and survival signals including CCL19, CCL21, IL-7, CXCL12 and hedgehog (Hh) ligands. Hh signaling is evolutionary conserved signaling pathway that serves several physiological and development processes mediated by externally secreted Hh ligands. We previously demonstrated that the canonical Hh ligand-PTCH1-SMO-GLI axis is functional and contributes to cell survival, proliferation and enhances chemo tolerance in DLBCL. We further showed that GLI1, Hh signaling transcription factor is aberrantly activated in ∼87% of DLBCL and this activation is in part mediated by sonic Hh ligands secreted by stromal cells. Although the importance of GLI1 in tumor development is well recognized, the molecular mechanisms controlling the transcriptional activity of GLI1 is limited. To identify regulatory components that participate in the transcriptional activity of GLI1, we explored GLI1 putative interacting proteins by liquid chromatography tandem mass spectrometry following immunoprecipitation of endogenous GLI1. We identified the inhibitor of NF-ĸB kinase, IKKβ as a novel GLI1-binding protein. In addition, we found that the kinase activity of IKKβ is critical to recruit and phosphorylate GLI1 in the C-terminal fragment. We further showed that in DLBCL cells stimulated with TNFα, IKKβ phosphorylates GLI1 and restricts the binding between GLI1 with HECT-type E3 ubiquitin ligase (ITCH) resulting in GLI1 stability and increased oncogenic potential. Inhibition of IKKβ-mediated GLI1 phosphorylation restored the binding between GLI1 and ITCH and promoted ubiquitination and degradation of GLI1. Collectively, these results indicate that IKKβ regulates the transcriptional activity of GLI1 by phosphorylating GLI1 and modulating the binding between GLI1 and ITCH. In DLBCL, canonical NF-κB and GLI1 mediated Hh signaling pathways are strongly responsive with tumor microenvironment; our study will help to understand the cross talk between these two pathways which could represents a novel therapeutic approach for DLBCL. Citation Format: Nitin K. Agarwal, Kranthi Kunkalla, Francisco Vega. The inhibitor of NF-ĸB kinase, IKKβ, regulates the stability of GLI1 transcription factor. [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 3605. doi:10.1158/1538-7445.AM2014-3605
Evidence for Rhythms of Mitotic Activity in Normal and Adenocarcinoma Cells of the Renal Tubules of Rana pipiens2
Authors: Patricia B. Marlow, Sherwin Mizell
Journal: JNCI Journal of the National Cancer Institute (1976)

Kidneys were studied from 1,111 leopard frogs (Rana pipiens) after exposures to a 12-hour light-12-hour dark environment. Circadian mitotic rhythms were observed in cells of normal and spontaneous adenocarcinomatous proximal convoluted tubules from these animals. Student's t-tests verified the existence of two distinct cell populations, normal and adenocarcinomatous, in the proximal tubules. Both the mitotic variations and the t-test values were significant with P values of 0.05 or less. Mean mitotic values for the normal and spontaneous adenocarcinomatous proximal tubule epithelia were generally lower during the light-phase and higher during the dark-phase periods of the control day. The mitotic rhythm of the cancerous epithelium was almost always superimposable in outline over that of the normal epithelium obtained during the same experimental period; i.e., the correspondence of phases of the normal and cancerous mitoses was almost identical in a single graph, although the amplitude of the cancerous mitoses was always higher. In addition to the reproducible circadian rhythms, the data demonstrated evidence for the existence of ultradian, as well as circannual rhythms.
Abstract P3-06-20: A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer
Authors: Yeon Hee Park, Hae Hyun Jung, In-Gu Do, Eun Yoon Cho, Insuk Sohn, Sin-Ho Jung, Won Ho Kil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im
Journal: Cancer Research (2015)

Abstract BACKGROUND: Women with triple-negative breast cancers (TNBCs) represent a significant treatment challenge as they have a relatively poor prognosis and no effective targeted therapy exists. Although TNBCs are often discussed as a single disease entity of breast cancers, in fact they are very heterogeneous. The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate TNBCs among patients, who received adjuvant chemotherapy after curative surgery, into those with high or low risk for distant recurrence. METHODS: We tested whether the results of a NanoString expression assay that targeted 245 prospectively selected genes and used mRNA extracted from paraffin wax-embedded tumor tissues would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). RESULTS: NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63, and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis in this patients’ cohort and were validated with cross-validation. The proportions of patients categorized as having low or high risk were 75% and 25%, respectively. The Kaplan–Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% (95% CI, 48.6–78.9%) and 85% (95% confidence interval, CI, 79.2–90.7%), respectively. When adjusting for tumor–node–metastasis (TNM) stage, the distant recurrence-free survival (DRFS)s in the low-risk groups were significantly longer than that in the high-risk group (p&amp;lt;.001) in each of TNM stages I plus II, and III. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. CONCLUSION: A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy. Citation Format: Yeon Hee Park, Hae Hyun Jung, In-Gu Do, Eun Yoon Cho, Insuk Sohn, Sin-Ho Jung, Won Ho Kil, Seok Won Kim, Jeong Eon Lee, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im. A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers (TNBCs) who receive adjuvant chemotherapy following curative surgery of the primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-20.
Characteristics and significance of untreated major depressive disorder
Authors: W Coryell, J Endicott, G Winokur, H Akiskal, D Solomon, A Leon, T Mueller, T Shea
Journal: American Journal of Psychiatry (1995)

This study sought to describe the characteristics and consequences of untreated major depressive disorder.As part of a family study of probands with major affective disorders, raters assessed 3,119 first-degree relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these individuals were reassessed 6 years later, 547 had experienced episodes of major depressive disorder in the interval. Those who had sought any form of treatment for any episode of major depressive disorder in the interval were compared, by baseline demographic characteristics and clinical features of their worst episodes of major depressive disorder, to those who had not. Individuals who had had untreated major depressive disorder were then compared, by changes in socioeconomic status and by levels of psychosocial impairment at follow-up, to a matched group with no major depressive disorder in the interval.The worst episodes of 313 treated individuals, compared to those of 234 untreated individuals, were characterized by older age, symptoms of the endogenous subtype, longer durations, and the presence of disruption in role function. Each of these factors contributed independently to the distinction between treated and untreated episodes. Untreated individuals experienced significant psychosocial impairment on follow-up but did not show the economic disadvantages shown elsewhere for probands who began follow-up as they sought treatment at tertiary medical centers.These data suggest that illness characteristics and age determine the decision to seek treatment for major depressive disorder. Untreated depression is apparently associated with long-standing psychosocial difficulties but not with serious economic consequences.
Negative Remodeling and Calcified Plaque in Octogenarians With Acute Myocardial Infarction
Authors: Salah-Eddine Hassani, Gary S. Mintz, Helen S. Fong, Sang-Wook Kim, Zhenyi Xue, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, William O. Suddath, Ron Waksman, Neil J. Weissman
Journal: Journal of the American College of Cardiology (2006)
Application of Monodirectional Janus Patch to Oromucosal Delivery System
Authors: Jae Bem You, Ah Young Choi, Jieung Baek, Myung Seok Oh, Sung Gap Im, Kyung Eun Lee, Hye Sun Gwak
Journal: Advanced Healthcare Materials (2015)

Drug delivery through mucosae has received huge research attention owing to its advantageous characteristics such as accurate dose control and the avoidance of premature metabolism of vulnerable drugs by oral administration. However, body fluid in mucosae may dissolve the drug, releasing it to unwanted directions. Here, a Janus drug delivery patch with monodirectional diffusion property is devised to deliver drugs efficiently and to overcome the issue of unwanted drug release. A polyester fabric is coated with a hydrophobic polymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10‐heptadecafluorodecyl methacrylate), via initiated chemical vapor deposition. Subsequently, hydrophilicity is rendered selectively on one surface by base‐catalyzed hydrolysis to obtain a Janus substrate with both hydrophobic and hydrophilic surfaces. The hydrophilic surface of the Janus substrate is further coated with resveratrol‐loaded hydrogel to produce a Janus drug delivery patch. The fabricated patch efficiently blocks fluid penetration from one side to the other in mucous environment. Delivery of resveratrol through hairless mouse skin and reconstructed human mucosae using Janus patch shows higher permeation flux compared to bare control patch. The Janus drug delivery patch shown in this study can be a useful tool for efficient transmucosal delivery of various kinds of drugs.
Abstract 3638: Vaccine-draining lymph nodes of cancer patients for generating anticancer antibodies
Authors: Girja S. Shukla, Stephanie C. Pero, Yu-jing Sun, Chelsea L. Carman, Walter C. Olson, Craig L. Slingluff, David N. Krag
Journal: Cancer Research (2014)

Abstract Human vaccine studies regularly demonstrate vaccine-induced antibodies in the blood. Characterization of these antibodies shows that they exhibit an extensive range of bioactive mechanisms. Unfortunately, there is not yet a reliable method by which to produce these important antibodies. Human antibodies may not require any molecular modification for therapeutic application and have a much faster pipeline to clinical studies than animal-derived antibodies. Lymph nodes are the primary destination of tumor or vaccine antigens. In the node, B cells undergo clonal expansion and somatic hypermutation, leading to the affinity-matured populations of effector B cells secreting antibodies that bind to the tumor or vaccine. The cancer vaccine-draining node is the ideal source of B cells that produce anticancer antibodies. Despite multiple human cancer vaccine studies, very little research has been done to recover the B cells responsible for vaccine-induced anticancer antibodies. In the present study, we used mononuclear cells from surgically removed vaccine-draining lymph nodes of melanoma patients vaccinated with 6 melanoma peptides derived from cancer-testis antigens and from melanocytic differentiation proteins for generating anti-vaccine peptide antibodies. The lymph node draining the vaccination site was localized by lymphatic mapping with a radiotracer. The development and maturity of B cells were assessed by determining phenotypic characters of lymph node cells using multicolor flow cytometry. The results showed that these vaccine-draining nodes contain high numbers of class-switched (CD19+CD27+IgD-IgM-) B cells and plasmablasts (CD19+CD38+IgM-). B-cell ELISpot assay was used to quantify the proportion of B cells in vaccine-draining lymph nodes that secrete anti-melanoma peptide antibodies. Positive ELISpot responses were observed in patients who also showed serum antibody-reactivity towards the vaccine peptides. The identification of lymph node cell samples exhibiting strong B-cell responses allows efficient generation and screening of hybridomas that secrete antibodies against cancer vaccine antigens. This study establishes a step-wise protocol for generating anti-cancer antibodies from vaccine-draining lymph nodes. We anticipate that the ability to reliably generate in vitro the same antibodies observed in the blood of vaccinated patients will further stimulate research to understand mechanisms of human antibody activity. Citation Format: Girja S. Shukla, Stephanie C. Pero, Yu-jing Sun, Chelsea L. Carman, Walter C. Olson, Craig L. Slingluff, David N. Krag. Vaccine-draining lymph nodes of cancer patients for generating anticancer antibodies. [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 3638. doi:10.1158/1538-7445.AM2014-3638
General practice at night
Authors: M. Shutkever
Journal: BMJ (1995)

EDITOR,--The title of a recent news item “GPs accept out of hours offer unanimously” would be humorous if it was not so tragically untrue.1 General practitioners have done no such thing. We have not even been asked if we accept the offer. A few months ago I was amazed at the response to a ballot, which showed that a huge majority of general practitioners were ready finally to unite against …
Abstract 706: Detailed Distribution of Acute Pulmonary Thromboemboli: Direct Evidence for Reduction of Acquisition Length and Radiation Dose for Triple Rule Out Computed Tomographic Angiography
Authors: Masae Uehara, Nobuhiro Tanabe, Nobusada Funabashi, Koichiro Tatsumi, Issei Komuro
Journal: Circulation (2009)

Purpose: To reduce the redundant acquisition range and total radiation dose for planning appropriate “Triple rule-out” computed tomographic (CT) angiography (CTA) for acute chest pain, we evaluated...