tbuckley/cabot-search huggingface dataset:
Confirmation of Gene Expression–Based Prediction of Survival in Non–Small Cell Lung Cancer
Authors: Nancy L. Guo, Ying-Wooi Wan, Kursad Tosun, Hong Lin, Zola Msiska, Daniel C. Flynn, Scot C. Remick, Val Vallyathan, Afshin Dowlati, Xianglin Shi, Vincent Castranova, David G. Beer, Yong Qian
Journal: Clinical Cancer Research (2008)

Abstract Purpose: It is a critical challenge to determine the risk of recurrence in early stage non–small cell lung cancer (NSCLC) patients. Accurate gene expression signatures are needed to classify patients into high- and low-risk groups to improve the selection of patients for adjuvant therapy. Experimental Design: Multiple published microarray data sets were used to evaluate our previously identified lung cancer prognostic gene signature. Expression of the signature genes was further validated with real-time reverse transcription-PCR and Western blot assays of snap-frozen lung cancer tumor tissues. Results: Our previously identified 35-gene signature stratified 264 patients with NSCLC into high- and low-risk groups with distinct overall survival rates (P &amp;lt; 0.05, Kaplan-Meier analysis, log-rank tests). The 35-gene signature further stratified patients with clinical stage 1A diseases into poor prognostic and good prognostic subgroups (P = 0.0007, Kaplan-Meier analysis, log-rank tests). This signature is independent of other prognostic factors for NSCLC, including age, sex, tumor differentiation, tumor grade, and tumor stage. The expression of the signature genes was validated with real-time reverse transcription-PCR analysis of lung cancer tumor specimens. Protein expression of two signature genes, TAL2 and ILF3, was confirmed in lung adenocarcinoma tumors by using Western blot analysis. These two biomarkers showed correlated mRNA and protein overexpression in lung cancer development and progression. Conclusions: The results indicate that the identified 35-gene signature is an accurate predictor of survival in NSCLC. It provides independent prognostic information in addition to traditional clinicopathologic criteria.
Sclerotherapy of Bleeding Esophageal Varices in Schistosomiasis
Authors: P. Sakai, S. Boaventura, S. Ishioka, S. Mies, H. Sette Jr., H. W. Pinotti
Journal: Endoscopy (1990)

Ninety-seven patients with bleeding esophageal varices due to mansonic schistosomiasis were treated with endoscopic sclerotherapy. Seventy-five patients (Group I) had previously undergone surgery for portal hypertension and presented with bleeding recurrence. Twenty-two patients (Group II) had not undergone surgical treatment. The sclerotherapy technique employed was intravascular (IV) injections of ethanolamine in 40 patients and paravascular (PV) in 57 patients. Of a total of 38 (39 %) patients who had bleeding recurrence, 27 (36 %) were from Group I and II (50 %) from Group II (p < 0.005). Over a follow-up period of 48 to 132 months, 367 sessions of sclerotherapy were carried out in the 72 remaining patients from Group I (4.93 ± 2.05). The remaining 16 patients from Group II needed 121 (7.56 ± 2.70) sessions of sclerotherapy (p < 0.001). Thus, sclerotherapy was effective in the control of rebleeding in 73 (97.3 %) patients from Group I and 16 (72.7 %) from Group II (p < 0.05). We conclude that previous surgical treatment for portal hypertension in patients with mansonic schistosomiasis, greatly benefits treatment of rebleeding esophageal varices by endoscopic sclerotherapy. This is probably due to the lower portal pressure after splenectomy.
A Multicenter, Phase II, Randomized, Noncomparative Clinical Trial of Radiation and Temozolomide with or without Vandetanib in Newly Diagnosed Glioblastoma Patients
Authors: Eudocia Q. Lee, Thomas J. Kaley, Dan G. Duda, David Schiff, Andrew B. Lassman, Eric T. Wong, Tom Mikkelsen, Benjamin W. Purow, Alona Muzikansky, Marek Ancukiewicz, Jason T. Huse, Shakti Ramkissoon, Jan Drappatz, Andrew D. Norden, Rameen Beroukhim, Stephanie E. Weiss, Brian M. Alexander, Christine S. McCluskey, Mary Gerard, Katrina H. Smith, Rakesh K. Jain, Tracy T. Batchelor, Keith L. Ligon, Patrick Y. Wen
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Vandetanib, a tyrosine kinase inhibitor of KDR (VEGFR2), EGFR, and RET, may enhance sensitivity to chemotherapy and radiation. We conducted a randomized, noncomparative, phase II study of radiation (RT) and temozolomide with or without vandetanib in patients with newly diagnosed glioblastoma (GBM). Experimental Design: We planned to randomize a total of 114 newly diagnosed GBM patients in a ratio of 2:1 to standard RT and temozolomide with (76 patients) or without (38 patients) vandetanib 100 mg daily. Patients with age ≥ 18 years, Karnofsky performance status (KPS) ≥ 60, and not on enzyme-inducing antiepileptics were eligible. Primary endpoint was median overall survival (OS) from the date of randomization. Secondary endpoints included median progression-free survival (PFS), 12-month PFS, and safety. Correlative studies included pharmacokinetics as well as tissue and serum biomarker analysis. Results: The study was terminated early for futility based on the results of an interim analysis. We enrolled 106 patients (36 in the RT/temozolomide arm and 70 in the vandetanib/RT/temozolomide arm). Median OS was 15.9 months [95% confidence interval (CI), 11.0–22.5 months] in the RT/temozolomide arm and 16.6 months (95% CI, 14.9–20.1 months) in the vandetanib/RT/temozolomide (log-rank P = 0.75). Conclusions: The addition of vandetanib at a dose of 100 mg daily to standard chemoradiation in patients with newly diagnosed GBM or gliosarcoma was associated with potential pharmacodynamic biomarker changes and was reasonably well tolerated. However, the regimen did not significantly prolong OS compared with the parallel control arm, leading to early termination of the study. Clin Cancer Res; 21(16); 3610–8. ©2015 AACR.
Abstract IA7: Unraveling the complexities of p63 in cancer and stem cells
Authors: Elsa R. Flores
Journal: Cancer Research (2012)

Abstract Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including in cancer and the regulation of stem cells, but the mechanisms governing this are not clearly understood. We have generated conditional knockout mice that allow the functional separation of TAp63 and ΔNp63. Using the TAp63 conditional knock out mouse model, we found that TAp63 suppresses tumorigenesis and metastasis through coordinate transcriptional regulation of Dicer and miR-130b. Interestingly, we have recently found that ΔNp63 also plays an important role in miRNA processing by transcriptionally activating DGCR8. In turn, DGCR8 is required for processing of key miRNAs that repress genes required for stem cell pluripotency, Oct4, Sox2, and Nanog. Strikingly, epidermal cells derived from ΔNp63 deficient mice express markers of pluripotency at levels comparable to mouse embryonic stem cells. Moreover, these cells exhibit characteristics of stem cells that can self-renew and can differentiate into multiple cell fates in vitro and in vivo. Our data reveal a novel role for ΔNp63 in the commitment to epidermal differentiation through transcriptional regulation of DGCR8 and downstream modulation of key miRNAs required to maintain stem cell pluripotency. Taken together, our data show that p63 plays critical roles in regulating miRNAs in multiple biological processes. Citation Format: Elsa R. Flores. Unraveling the complexities of p63 in cancer and stem cells [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA7.
Monoclonal antibody with hemagglutination, immobilization, and neutralization activities defines an immunodominant, 47,000 mol wt, surface-exposed immunogen of Treponema pallidum (Nichols).
Authors: S A Jones, K S Marchitto, J N Miller, M V Norgard
Journal: The Journal of Experimental Medicine (1984)

Radioimmunoprecipitation (RIP) analyses performed on 125I-surface-labeled Treponema pallidum cells using various immune sera revealed the presence of six major surface antigens (immunogens) with apparent molecular weights of 47 K, 36 K, 34 K, 32 K, 29 K, and 13 K. Among these, the 47 K surface antigen was most abundant. Radioimmunoprecipitation assays using 125I-labeled T. phagedenis biotype Reiter or immunoblot analyses using the same strain, failed to reveal the presence of the 47 K mol wt antigen in the representative nonpathogenic treponeme. Preabsorption of anti-T. pallidum immune rabbit serum (IRS) with the Reiter organism did not remove anti-T. pallidum antibodies from immune serum that reacted with the 47 K mol wt immunogen or other immunogens of T. pallidum present in the characteristic antigenic profile. Monoclonal antibodies (mAb) directed specifically against the 47 K mol wt immunogen of T. pallidum also failed to react with an analogous 47 K mol wt component in Treponema phagedenis biotype Reiter, further suggesting the unique presence of this antigen in pathogenic treponemes. The presence of the 47 K mol wt surface immunogen in pathogenic treponemes other than T. pallidum subspecies pallidum was also observed (43). Anti-47 K immunogen mAb was nonreactive against rabbit IgG or IgM. mAb directed specifically against the 47 K mol wt immunogen of T. pallidum was examined for strategic functional activities. It was found to be reactive in the microhemagglutination assay for T. pallidum antibodies, the T. pallidum immobilization test, and was found to be capable of significant blockage of attachment of virulent T. pallidum to host cells in tissue culture. Additional significant biological activity for the anti-47 K mol wt immunogen mAb was revealed through results of the in vitro-in vivo neutralization test of Bishop and Miller, in which a 99% or 100% neutralizing activity was demonstrated. The combined data of this study suggest that the 47 K mol wt immunogen of T. pallidum represents an abundant, immunodominant, surface-exposed immunogen possessing potential biological importance in the pathogenesis and immunology of T. pallidum infection. These studies serve to establish the first functionally defined immunogen for T. pallidum, which may represent the major immunogen of the organism.
Assessment of severity of mitral regurgitation by measuring regurgitant jet width at its origin with transesophageal Doppler color flow imaging.
Authors: C Tribouilloy, W F Shen, J P Quéré, J L Rey, D Choquet, H Dufossé, J P Lesbre
Journal: Circulation (1992)

The ability of transesophageal color Doppler echocardiography to provide high-resolution images of both cardiac structure and blood flow in real time is advantageous for many clinical purposes. This study was performed to determine the utility of the regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging in the assessment of severity of mitral regurgitation.Sixty-three consecutive patients with mitral regurgitation underwent transesophageal color Doppler examination, and the diameter of regurgitant jet at its origin was measured. Both right and left cardiac catheterizations were performed within 24 hours of Doppler studies, and angiographic grading of mitral regurgitation and regurgitant stroke volume were evaluated. There was a close relation between the jet diameter at its origin measured by transesophageal Doppler color flow imaging and the angiographic grade of mitral regurgitation (r = 0.86, p less than 0.001). A jet diameter of 5.5 mm or more identified severe mitral regurgitation (grade III or IV) with a sensitivity of 92%, specificity of 92%, and positive and negative predictive values of 88% and 95%, respectively. In 31 patients with isolated mitral regurgitation, the jet diameter correlated well with the regurgitant stroke volume determined by a combined hemodynamic-angiographic method (r = 0.85, p less than 0.001). A jet diameter of 5.5 mm or more identified a regurgitant stroke volume of 60 ml or more with a sensitivity of 88%, specificity of 93%, and positive and negative predictive values of 94% and 87%, respectively.The regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging provides a simple and useful method of measuring the severity of mitral regurgitation, and it may allow differentiation between mild and severe mitral regurgitation.
Inherited Abnormality of Thyroxine-Binding Globulin with No Demonstrable Thyroxine-Binding Activity and High Serum Levels of Denatured Thyroxine-Binding Globulin
Authors: Yoshiharu Murata, Junta Takamatsu, Samuel Refetoff
Journal: New England Journal of Medicine (1986)

THYROID hormones (thyroxine and triiodothyronine) are transported in blood bound to serum proteins.1 2 3 The principal protein, which carries approximately 75 percent of the total thyroxine and triiodothyronine in serum, is thyroxine-binding globulin (TBG), an acidic glycoprotein of hepatic origin:4 , 5 Although wide changes in the concentration of TBG do not alter metabolic status, they do affect the concentration of thyroxine and triiodothyronine in serum.Five distinct types of inherited TBG variants have been described in humans. All follow an X-linked mode of inheritance.6 7 8 9 The three TBG variants that are believed to be quantitative are widely distributed among ethnic groups and all . . .
Distribution of caffeine levels in urine in different sports in India
Authors: Sachin Dubey, Tejinder Kaur, Shila Jain, Alka Beotra
Journal: British Journal of Sports Medicine (2010)

Caffeine (1,3,7-trimethylxanthine) is a xanthine alkaloid compound that acts as a stimulant and was banned for use in sports. Caffeine was removed from the World Anti-Doping Agency (WADA) prohibited list from January 2004. As per the requirement of WADA, the WADA-accredited labs are monitoring the presence of caffeine for signs of possible abuse. National Dope Testing Laboratory (NDTL), India, is monitoring caffeine levels in in-competition urine samples of sports persons from different sports disciplines. The aim of the present study is to find the distribution of caffeine levels in urine in different sport disciplines in Indian and other south-east Asian countries. Caffeine was measured using an alkaline extraction with tertiary butyl methyl ether followed by gas chromatographic nitrogen-phosphorus specific detection. A comparison of statistical data from the urine samples done from January 2008 to July 2010 in NDTL, India, for different discipline of sports since January 2008 to July 2010 was performed. The study proves beneficial in monitoring the abuse of caffeine in different disciplines of sports.
Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia
Authors: Shao-Qing Kuang, Hao Bai, Zhi-Hong Fang, Gonzalo Lopez, Hui Yang, Weigang Tong, Zack Z. Wang, Guillermo Garcia-Manero
Journal: Blood (2010)
TCT-801 Safety, Feasibility And Efficacy Of Transapical Off-Pump Mitral Valve Repair With Neochord Implantation
Authors: Andrea Colli, Erica Manzan, Fabio Zucchetta, Cristiano Sarais, Demetrio Pittarello, Gino Gerosa
Journal: Journal of the American College of Cardiology (2014)
Caveolin-1, Mammary Stem Cells, and Estrogen-Dependent Breast Cancers
Authors: Federica Sotgia, Hallgeir Rui, Gloria Bonuccelli, Isabelle Mercier, Richard G. Pestell, Michael P. Lisanti
Journal: Cancer Research (2006)

Abstract Estrogen exposure is considered a significant risk factor for breast cancer development. Estrogen receptor (ER) α is expressed at low levels in normal epithelia, and its expression is dramatically up-regulated as transformation progresses during mammary hyperplasia and adenocarcinoma development. The mechanism(s) driving ERα up-regulation during mammary tumorigenesis remains unclear. Caveolin-1 (Cav-1) is the structural protein of plasmalemmal invaginations, termed caveolae, which functions as a tumor suppressor gene. Interestingly, Cav-1 dominant-negative mutations are exclusively found in ERα-positive breast cancer samples. In support of these clinical findings, ERα expression is increased in Cav-1 (−/−) null mammary epithelia, and estrogen stimulation further enhances the growth of Cav-1-deficient three-dimensional epithelial structures. These phenotypes correlate with augmented levels of cyclin D1. In addition, Cav-1 gene inactivation induces the accumulation of a cell population with the characteristics of adult mammary stem cells. Primary cultures of Cav-1 (−/−) mammary epithelial cells exhibit premalignant changes, such as abnormal lumen formation, epidermal growth factor–independent growth, defects in cell substrate attachment, and increased cell invasiveness. Thus, Cav-1 gene inactivation promotes premalignant alterations in mammary epithelia and induces increased ERα expression levels and the up-regulation of cyclin D1. As tumor formation is a multihit process, Cav-1 mutations that occur during the early stages of mammary transformation may be a critical upstream/initiating event leading to increased ERα levels. (Cancer Res 2006; 66(22): 10647-51)
926 Influence of adhesion molecule deletion on hepatic listeriosis in mice
Authors: C RIVERA, W ARIAS, M TCHARMTCHI, C SMITH
Journal: Hepatology (2003)

Background/Aims: The injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induced an autoimmune graft-versus-host reaction (GVHR) which is analogous to autoimmune liver diseases. The interaction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) has been known to be profoundly involved in the trafficking of lymphocytes into the inflammatory tissues. The aim of this study was to clarify the role of VLA-4 or VCAM-1 in the development of GVHR-induced hepatic lesions in our model.Methods: B6 T spleen cells were injected into (B6.C-H-2bm12×B6) F1 mice intravenously. Anti-VLA-4 mAbs and/or anti-VCAM-1 mAbs were injected intraperitoneally at a dose of 2.5 mg/kg of each mAbs per body weight of mouse. We examined the changes in GVHR-induced hepatic lesions, serum levels of antimitochondrial antibodies (AMA) and cytokine mRNA expressions of liver-infiltrating lymphocytes using H.E. and immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-poly-merase chain reaction (RT-PCR), respectively.Results: Hepatic lesions of anti-VLA-4 mAbs-treated mice were inhibited compared with those of GVHR mice. However, the administration of mAbs did not interfere with the induction of splenomegaly, the invasion of CD4+, CD8+, B220+, or Mac-1+ cells around bile ducts, nor the production of AMA. Liver-infiltrating CD4+ T cells obtained from these treated mice did not alter the expression of T helper (Th)1 and Th2 cytokine mRNA.Conclusion: The results suggest that treatment with antibodies against these adhesion molecules could inhibit the infiltration of lymphocytes without affecting the Th1/Th2 balance. The blockade of VLA-4-mediated cell infiltration into the liver in this model may have a possible novel therapeutic role of VLA-4 mAbs.
A Review of the First 10 Years of Critical Care Aeromedical Transport During Operation Iraqi Freedom and Operation Enduring Freedom
Authors: Nichole Ingalls, David Zonies, Jeffrey A. Bailey, Kathleen D. Martin, Bart O. Iddins, Paul K. Carlton, Dennis Hanseman, Richard Branson, Warren Dorlac, Jay Johannigman
Journal: JAMA Surgery (2014)

Advances in the care of the injured patient are perhaps the only benefit of military conflict. One of the unique aspects of the military medical care system that emerged during Operation Iraqi Freedom and Operation Enduring Freedom has been the opportunity to apply existing civilian trauma system standards to the provision of combat casualty care across an evolving theater of operations.To identify differences in mortality for soldiers undergoing early and rapid evacuation from the combat theater and to evaluate the capabilities of the Critical Care Air Transport Team (CCATT) and Joint Theater Trauma Registry databases to provide adequate data to support future initiatives for improvement of performance.Retrospective review of CCATT records and the Joint Theater Trauma Registry from September 11, 2001, to December 31, 2010, for the in-theater military medicine health system, including centers in Iraq, Afghanistan, and Germany. Of 2899 CCATT transport records, those for 975 individuals had all the required data elements.Rapid evacuation by the CCATT.Survival as a function of time from injury to arrival at the role IV facility at Landstuhl Regional Medical Center.The patient cohort demonstrated a mean Injury Severity Score of 23.7 and an overall 30-day mortality of 2.1%. Mortality en route was less than 0.02%. Statistically significant differences between survivors and decedents with respect to the Injury Severity Score (mean [SD], 23.4 [12.4] vs 37.7 [16.5]; P < .001), cumulative volume of blood transfused among the patients in each group who received a transfusion (P < .001), worst base deficit (mean [SD], -3.4 [5.0] vs -7.8 [6.9]; P = .02), and worst international normalized ratio (median [interquartile range], 1.2 [1.0-1.4] vs 1.4 [1.1-2.2]; P = .03) were observed. We found no statistically significant difference between survivors and decedents with respect to time from injury to arrival at definitive care.Rapid movement of critically injured casualties within hours of wounding appears to be effective, with a minimal mortality incurred during movement and overall 30-day mortality. We found no association between the duration of time from wounding to arrival at Landstuhl Regional Medical Center with respect to mortality.