tbuckley/cabot-search huggingface dataset:
Abstract 3690: MMP-1 and pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer
Authors: Benjamin C. Lin, Xiangnan Du, Qian-Rena Wang, Hao Li, Ellen Ingalla, Janet Tien, Isabelle Rooney, Avi Ashkenazi, Elicia Penuel, Jing Qing
Journal: Cancer Research (2014)

Abstract Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) via overexpression or mutation occurs frequently in bladder cancer, and experimental therapeutic agents have entered into clinical trials to evaluate the potential activity of FGFR3-targeted therapy in this disease. However, a convenient accessible biomarker indicative of targeted pathway modulation in vivo drug activity is urgently needed. Through transcriptional profiling of bladder carcinoma cells expressing inducible FGFR3 short hairpin RNAs, we identified two matrix metalloproteinases (MMPs), MMP-1 and MMP-10, as potential downstream targets of FGFR3. We found that FGFR3 signaling promotes expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. FGFR3 inhibition by an investigational anti-FGFR3 human monoclonal antibody, R3Mab, in bladder cancer xenograft models substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, we detected elevated levels of both MMP-1 and pro-MMP-10 in the urine of patients with advanced bladder cancer. In a phase 1 dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in bladder cancer patients. Together, these findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for FGFR3-targeted therapy in bladder cancer. Citation Format: Benjamin C. Lin, Xiangnan Du, Qian-Rena Wang, Hao Li, Ellen Ingalla, Janet Tien, Isabelle Rooney, Avi Ashkenazi, Elicia Penuel, Jing Qing. MMP-1 and pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer. [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 3690. doi:10.1158/1538-7445.AM2014-3690
Needlestick Bill Passes
Authors: Rebecca Voelker
Journal: JAMA (2000)

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
A polymorphism of the DNA repair enzyme XRCC1 is associated with treatment prediction in anthracycline and CMF-based chemotherapy of patients with primary invasive breast cancer
Authors: Christina Justenhoven, Malgorzata Jaremko, Werner Schroth, Benny K. Abraham, Peter Fritz, Caren Vollmert, Thomas Illig, Wolfgang Simon, Matthias Schwab, Hiltrud B. Brauch
Journal: Clinical Cancer Research (2006)

B42  Outcome and survival in anthracycline- and cyclophosphamide/methotrexate/5-fluorouracil (CMF)-based chemotherapy of invasive breast cancer are unpredictable. Insights into treatment prediction are expected from studies searching for an association between genetic polymorphisms and treatment outcome effects. A common feature of treatment with chemo-reagents is therapeutically induced DNA damage. Therefore, we tested the hypothesis of a relationship between event-free survival and genotype distributions of 7 polymorphic DNA repair enzymes and 4 cell cycle regulators. Our retrospective case-case comparison included 180 female patients who had received adjuvant chemotherapy with anthracycline/cyclophosphamide or CMF upon dignosis of primary invasive breast cancer at the Robert Bosch Hospital Stuttgart between 1986 and 2000. There were 92 patients without recurrence and 88 with recurrences or reported dead. The median clinical follow-up was 61.7 months (range 7.6 to 201.8 months). Constitutional DNA was isolated from archived tissues and genotyped at 19 loci by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Statistical analyses included adjusted risk estimates, Kaplan-Meier analyses, Cox proportional hazard model, and permutation testing. Carriers of the XRCC1_1196_AA genotype had a reduced risk for recurrence/death (OR 0.16; 95% CI: 0.05-0.49) which was observed in the survival analysis of all patients (P = 0.003) and of patients treated with chemotherapy but not radiotherapy (P = 0.006). Multivariate analysis confirmed XRCC1 as a potential treatment predictor (HR 0.62; 95% CI: 0.43-0.89). The result was stable upon permutation testing. Polymorphisms at ERCC4 and CCND3 showed effects in univariate analyses but not in multivariate analyses. We conclude that the DNA repair enzyme XRCC1 is a potential treatment predictor for the outcome and survival of anthracycline and CMF-based chemotherapy of invasive breast cancer that should be followed up in prospective clinical trials.
Abstract 20114: Effect of Fenofibrate Therapy on Cardiovascular Disease in Men versus Women with Type 2 Diabetes in the ACCORD-Lipid Trial
Authors: Laura C Lovato, Marshall B Elam, Robert P Byington, Mary E Sweeney, JoAnn M Sperl-Hillen, Jerome Fleg, Daniel Weiss, Daniel L Lorber, Henry N Ginsberg
Journal: Circulation (2010)

Background: The ACCORD-Lipid trial assessed effects of combination fenofibrate and simvastatin therapy on cardiovascular disease (CVD) endpoints in Type 2 Diabetes (T2DM). There was no significant ...
Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism
Authors: M. Ibarrola-Villava, M. Martin-Gonzalez, P. Lazaro, A. Pizarro, A. Lluch, G. Ribas
Journal: British Journal of Dermatology (2012)

Background Glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. Objectives Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low-penetrance variants with a role in susceptibility to malignant melanoma (MM). Methods In this case–control study, 562 Spanish patients with sporadic MM and 338 cancer-free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real-time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs. Results The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06–1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42–8·09 and OR: 20·42, 95% CI: 2·80–417·42, respectively). Conclusions This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.
Abstract 1825: Jab1/Csn5 a new target in the resistant mechanism to HER2-targeted therapies for breast cancer
Authors: Francois X. Claret, Thuy Vu, Terry J. Shackleford, Jennifer Allensworth, Qingxiu Zhang, Ling Tian, Ronghua Zhang
Journal: Cancer Research (2014)

Abstract Her2 positive (Her2+) breast cancer (BC) accounts for 20% of all breast cancer subtypes and is associated with high risk of death. Trastuzumab (Ttzm), first FDA-approved targeted therapy for BC, represents a key milestone in the personalized treatment of Her2+ metastatic disease (MBC). However, 75% of Her2+ MBC are or become resistant to Ttzm and experience relapse or disease progression. This suggests that tumors acquire or possess an intrinsic mechanism of resistance that prevents from Her2 inhibition. Therefore, it is important to identify novel pathway to overcome the resistance. Recent studies have proposed various potential mechanisms leading to the resistance, including p27 rapid degradation. Jab1/Csn5 a novel candidate oncogene that we identified contributes to the progression of BC and is correlated with poor prognosis. Our study demonstrated that Jab1/Csn5 degrades p27 in MBC. These findings suggest that Jab1 overexpression contributes to Ttzm-resistance by facilitating p27-degradation. Jab1/Csn5 is overexpressed in 50% of primary and 90% of MBC while its expression is low or absent in normal adult breast tissues. We previously identified that high expression of Jab1 is associated with shorter progression-free survival in MBC patients. In this study, we showed that the knockdown of Jab1 sensitizes to Ttzm-treatment. Mechanistically, we found that Jab1/Csn5 overexpression is significantly correlated with the activation of Akt pathway in Her2+ MBC and xenograft models. Interestingly, activated Akt, due to PTEN-loss or PI3K activating mutation has been widely implicated in the potential mechanism to Ttzm-resistance. Therefore, our results suggest that targeting Jab1/Csn5 overcomes the resistance to Ttzm via interfering with PI3K/Akt pathway. Our study identifies Jab1 as a novel contributor to Ttzm-resistance and elucidates its potential mechanisms of actions. Jab1 could be used as a predictive marker of tumor response to Ttzm, which could assist clinicians in selecting the best treatment modalities for patients with MBC. Note: This abstract was not presented at the meeting. Citation Format: Francois X. Claret, Thuy Vu, Terry J. Shackleford, Jennifer Allensworth, Qingxiu Zhang, Ling Tian, Ronghua Zhang. Jab1/Csn5 a new target in the resistant mechanism to HER2-targeted therapies for breast cancer. [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 1825. doi:10.1158/1538-7445.AM2014-1825
TRANSIENT FUNCTIONAL A-V HEART BLOCK INDUCED BY THE SWALLOWING OF FOOD; CASE REPORT
Authors: Charles Shookhoff, Louis Blumenfeld
Journal: Annals of Internal Medicine (1939)

Case Reports1 August 1939TRANSIENT FUNCTIONAL A-V HEART BLOCK INDUCED BY THE SWALLOWING OF FOOD; CASE REPORTCHARLES SHOOKHOFF, M.D., F.A.C.P., LOUIS BLUMENFELD, M.D.CHARLES SHOOKHOFF, M.D., F.A.C.P.Search for more papers by this author, LOUIS BLUMENFELD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-2-345 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis case of functional heart block is being reported because we believe this syndrome, and especially milder manifestations of it, may not be as uncommon as the few cases reported would lead one to believe. Instances of Adams-Stokes syndrome, due to overstimulation of the vagus and without apparent cardiac pathology, have been reported as early as 1875 by Thanhoffer1and in 1898 by Neuburger and Edinger,2and others. It was not until 1934, when Weiss and Ferris3reported their thoroughly studied cases of syncope of reflex vagal origin—which they aptly termed "Vago-Vagal Syndrome"—that the present generation of physicians was reminded...Bibliography1. THANHOFFER : Centralbl. f. d. med. Wissensch., 1875, p. 405. Google Scholar2. NEUBURGEREDINGER TL: Einseitiger fast totaler Mangel des Cerebellums, Varix oblongatae, Herztod durch Accessoriusreizung, Berl. klin. Wchnschr., 1898, xxxv, 69. Google Scholar3. WEISSFERRIS SEB: Adams-Stokes syndrome with transient complete heart block of vagovagal reflex origin; mechanism and treatment, Arch. Int. Med., 1934, liv, 931. CrossrefGoogle Scholar4. IGLAUERSCHWARTZ SBA: Heart block periodically induced by the swallowing of food in a patient with cardiospasm, Ann. Otol., Rhinol., and Laryngol., 1936, xlv, 875. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York*Received for publication June 21, 1938.From the Cardiovascular Division of the Department of Internal Medicine (Dr. Simon R. Blatteis, Chief) and the Nose and Throat Department of the Jewish Hospital of Brooklyn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1939Volume 13, Issue 2Page: 345-351KeywordsCardiology and cardiovascular diseasesFoodHeartPharynxReflexesSwallowingSyncope ePublished: 1 December 2008 Issue Published: 1 August 1939 PDF downloadLoading ...
Abstract 6242: Comparison of Facilitated and Primary Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Yassir Nawaz, Jurga Adomaityte, Zishan K Siddiqui, Muhammed Amer, Rehan Qayyum
Journal: Circulation (2008)

Background: Facilitated percutaneous coronary intervention (PCI), in which pharmacological agents are administered before coronary angiography, may result in early restoration of myocardial perfusion and can improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). To examine whether facilitated PCI is associated with better myocardial perfusion and clinical outcomes than primary PCI, we performed a meta-analysis of the clinical trials that compared the two strategies. Methods: PubMed, EMBASE, and The Cochrane Collaboration databases were searched through June 2008. We included clinical trials that were published in English language peer-reviewed medical journals and randomized patients with STEMI to facilitated or primary PCI. Two investigators independently abstracted data. Random-effects model was used to pool results. Results: Of the 419 identified articles, 24 were included (total patients =7997, facilitated PCI =4409, primary PCI =3588, median age=61 years, males=78%). Facilitated PCI increased myocardial perfusion as measured by grade 2 and/or 3 myocardial blush (588 vs. 468, OR=1.66, 95%CI=1.19 to 2.32) and ST segment resolution (1021 vs. 790, OR=1.61, 95%CI=1.25 to 2.09) as compared to primary PCI. Facilitated PCI was similar to primary PCI in reducing mortality (238 vs. 215, OR=1.10, 95%CI=0.88 to 1.37), reinfarction (129 vs. 109, OR=1.16, 95%CI=1.16(0.87 to 1.55), target vessel revascularization (181 vs. 144, OR=1.34, 95%CI=0.88 to 2.04), and stroke (51 vs. 24, OR=1.99, 95%CI=0.85 to 4.66). However, facilitated PCI was associated with increased incidence of major bleeding (236 vs. 151, OR=1.42, 95%CI=1.12, 1.81). Conclusion: As compared to primary PCI, facilitated PCI is associated with early restoration of myocardial perfusion, but has no effect on overall mortality, reinfarction, target vessel revascularization, and stroke, and increases risk of major bleeding in patients with STEMI. Results of meta-analysis comparing facilitated and primary percutneous coronary intervention
Scientific method and raw data should be considered
Authors: N. T James
Journal: BMJ (1996)

EDITOR,—Proponents of evidence based medicine claim that it is the conscientious, explicit, and judicious use of current best available external evidence about medical care.1 What about scientific method and raw data? Scientific method—the fundamental intellectual activity of obtaining data, assessing them by a series of valid arguments, and obtaining a series of conclusions in descending order of likelihood in all subjects—does not seem to merit consideration.

Paradoxically, evidence based medicine seems to avoid all contact with the first hand evidence by replacing original findings with subjectively …
Comparison of i.v. quinidine and disopyramide.
Authors: R L Engler
Journal: Circulation (1980)

procainamide.We clearly showed in dogs1 and have recently confirmed in man2 that the two drugs have different electrophysiologic effects.Woosley et al.3 have recently reported that antiarrhythmic response to one drug does not necessarily mean response to the other.Thus, just because a patient responds to procainamide there is absolutely no guarantee that that patient will respond to NAPA, because the drugs probably have different mechanisms of action.To date there are only a small number of publications in relatively small numbers of patients indicating that NAPA is an efficacious antiarrhythmic agent.We would prefer to await the results of further clinical trials which might help to establish its appropriate role as an antiarrhythmic agent before recommending its widespread use.
Energy metabolism in human erythrocytes
Authors: Stephen A. Feig, George B. Segel, Stephen B. Shohet, David G. Nathan
Journal: Journal of Clinical Investigation (1972)

Normal red cells were incubated in the absence of glucose to develop a system in which total adenosine triphosphate (ATP) turnover could be assessed. After 1 hr, the triose pool had been completely consumed. Thereafter, the metabolism of 2,3-diphosphoglycerate (DPG) to pyruvate and lactate was the sole significant source of ATP synthesis.10(-3)M CuCl(2), which did not enter the cells, diminished ATP utilization by more than 50%. This could be only partially attributed to the inhibition by copper of residual acylation and cation pumping, which were already reduced by glucose depletion. Other membrane enzymes, which presumably function in the maintenance of membrane integrity, must, therefore, use a significant portion of erythrocyte ATP. The behavior of glucose-depleted red cells with respect to cation transport was complex. The addition of ouabain did not decrease ATP utilization in these red cells. Ouabain inhibitable potassium influx was nearly normal after triose depletion, but total potassium influx was decreased. In contrast, the ouabain inhibitable sodium efflux was markedly reduced after triose depletion, although the concentration of ATP was 70% of normal. The dissociation of monovalent cation pumping suggests that the energy for active sodium transport is derived from a specific source (such as the ATP produced by the phosphoglycerate kinase reaction) distinct from that for potassium transport.
45. Adenoviral tetanus toxin light chain gene expression in the brainstem induces specific motor inhibition
Authors: Ajit A. Krishnaney, Zuowei Zhao, Qingshang Teng, James Liu, Diana Tenase, Mary Garrity-Moses, Michael Davis, Nicholas M. Boulis
Journal: Molecular Therapy (2004)

Introduction: Focused neural inhibition is an important potential therapy for neural disorders that stem from an imbalance in neural activity. Gene based delivery of neuromodulators such as the tetanus toxin light chain fragment (TeTxLC), could help rectify these imbalances with inherent advantages over currently available methods.
Patellofemoral pain syndrome
Authors: C N. van Dijk, W. M van der Tempel
Journal: BMJ (2008)

Usually resolves over time, and intervention offers only limited benefit

Patellofemoral pain syndrome is defined as pain behind or around the patella caused by stress in the patellofemoral joint. Symptoms are usually provoked by climbing stairs, squatting, and sitting with flexed knees for long periods of time. It is a common presentation in general practice and can have a big effect on patients’ ability to work.1 Physiotherapy and foot orthoses available without prescription are often used in the management of patellofemoral pain syndrome. In the linked randomised controlled trial (doi:10.1136/bmj.a1735), Collins and colleagues assess the effectiveness of foot orthoses, flat insoles, multimodal physiotherapy (patellofemoral joint mobilisation, patellar taping, quadriceps muscle retraining, and education), or a combination of foot orthoses and physiotherapy in people with this syndrome.2

The rationale for treatment is to correct unbalanced tracking of the patella. Knee braces, knee taping, knee sleeves, and …
Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains: a clinical and histological comparison. Dermatological Surgery and Lasers
Authors: D.W. Edstrom, M-A. Hedblad, A-M. Ros
Journal: British Journal of Dermatology (2002)

Journal Article Flashlamp pulsed dye laser and argon‐pumped dye laser in the treatment of port‐wine stains: a clinical and histological comparison Get access D.W. Edström, D.W. Edström Department of Dermatology, Karolinska Hospital, S‐171 76 Stockholm, Sweden Desiree Wiegleb Edström.E‐mail: desiree.edstrom@ks.se Search for other works by this author on: Oxford Academic Google Scholar M‐A. Hedblad, M‐A. Hedblad Department of Dermatology, Karolinska Hospital, S‐171 76 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar A‐M. Ros A‐M. Ros Department of Dermatology, Karolinska Hospital, S‐171 76 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 2, 1 February 2002, Pages 285–289, https://doi.org/10.1046/j.1365-2133.2002.04470.x Published: 01 February 2002 Article history Accepted: 19 July 2001 Published: 01 February 2002
Doctors in the Great War
Authors: Linda Bryder
Journal: BMJ (2001)

Ian R Whitehead Leo Cooper, £25, pp 309 ISBN 0 85052 691 4

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Many books have been written about the first world war, but few have addressed medical experiences. Ian Whitehead, a lecturer in modern British history, wrote his PhD thesis on medical officers and the British army during the first world war, which forms the basis of this book. Well researched and documented, the text is complemented by 20 photographs reproduced from collections held at the Imperial War …

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Adenovirus Vector-Based Purging of Multiple Myeloma Cells
Authors: Gerrard Teoh, Ling Chen, Mitsuyoshi Urashima, Yu-Tzu Tai, Leo A. Celi, Dongshu Chen, Dharminder Chauhan, Atsushi Ogata, Robert W. Finberg, Iain J. Webb, Donald W. Kufe, Kenneth C. Anderson
Journal: Blood (1998)