tbuckley/cabot-search huggingface dataset:
Abstract 2219: Development of an assay to detect transcription misincorporation errors in Escherichia coli
Authors: Jorge A. Irizarry-Caro, Mary Ernst, Carolyn Court, Alison Rattray, Mikhail Bubunenko, Ding Jin, Donald Court, Jeffrey Strathern
Journal: Cancer Research (2015)

Abstract In contrast to errors in DNA replication which can product heritable mutations, errors in transcription cause only transient alterations. The temporary nature of these transcription mistakes has made them difficult to detect and genetic screens to identify mutations that lower the fidelity of transcription have been problematic. We addressed this problem by developing methods to turn transient transcription errors into permanent genetic changes. The principle is based on suppression of a mutation in the active site of the cre recombinase. This assay is based on two parts: a source of Cre, which is actually the transcription misincorporation substrate, and a genetic reporter with a phenotypic change created by Cre-mediated recombination between lox sites. To develop a substrate for E. coli we chose the galactokinase gene (galK) as our reporter. From an alignment of the galK protein from E.coli, H. sapiens and L. lactis we identified sites that might be able to accept a 12aa insertion encoded by the LoxP sequence without disrupting its function. We selected four different sites that were away from the GalK active site and on the surface of the protein. We started our project using the strain MG1655, which is galK (+), able to grow in galactose as a carbon source and red on a MacConkey galactose plate (MAcGal). Using oligo recombineering, we first inserted a 7 base sequence, which caused a frame-shift mutation, the cells became galK (-) and, therefore white on MacGal. To put it back in frame, we next replaced the 7 bases with a 36 base loxP site, which, if it does not disrupt the function of galK will make the cells galK (+) again. To our surprise, the insertion of this LoxP site was completely successful, putting the gene back in frame and making the cells galK (+) and, therefore, red at each of the four sites we chose. A derivative of this reporter was made with the a portion of the galK gene inverted at one of the loxP sites. Active Cre recombinase can be detected by flipping the inversion to restore galK function. The active site mutant cre-Y324C exhibits a very low inversion rate. Mutations that reduce the accuracy of transcription, such as cells defective in greA, exhibit an elevated frequency of galK (+) inversions. This system will be used to identify additional mutations that reduce the fidelity of transcription in E. coli. Citation Format: Jorge A. Irizarry-Caro, Mary Ernst, Carolyn Court, Alison Rattray, Mikhail Bubunenko, Ding Jin, Donald Court, Jeffrey Strathern. Development of an assay to detect transcription misincorporation errors in Escherichia coli. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2219. doi:10.1158/1538-7445.AM2015-2219
Abstract 1180: Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival
Authors: Nelson Ho, Brenda L. Coomber
Journal: Cancer Research (2015)

Abstract The Warburg Effect describes the widely observed metabolic phenotype of cancer cells and their heavy reliance on the glycolytic pathway for energy production regardless of oxygen tension. This is a result of alterations to metabolic signaling pathways leading to an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. 3-bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of targeting critical metabolic pathways in cancer cells. Here we examine the importance of HKII to cell proliferation and survival and also whether its inhibition could provide a therapeutic strategy in human colorectal cancer (CRC). Initially, established human CRC cell lines (HCT116, Caco2, SW480, DLD-1) were screened for HKII mRNA and protein expression. Cell proliferation and survival following HKII inhibition via both siRNA and 3BP treatment was determined using crystal violet staining, flow cytometry and western blotting. Sensitivity to 3BP was correlated with HKII expression amongst the cell lines screened. We next examined the pro-survival AKT signaling pathway via western blotting and found that AKT phosphorylation was dependent on 3BP dose and was residue-specific. Immunofluorescence was then used to examine subcellular HKII localization. Following 3BP treatment, mitochondrial localization of HKII was lost. As a result of tumor vascular abnormalities, regions within a tumor are exposed to transient and/or chronic ischemia, resulting in altered oxygen and nutrient availablity. To examine the effects of glucose availability on 3BP sensitivity, media glucose was gradually reduced in a step-wise manner and HKII expression, cell proliferation and cell survival were evaluated in CRC cell lines. Cells grown under reduced or normal glucose conditions were less sensitive to 3BP exposure than cells grown under high glucose conditions, and responses correlated with changes in HKII expression. Using immunostaining, we examined the expression of HKII in both normoxic and ischemic regions in FFPE samples of human CRC. These results were correlated to tumor stage and grade, along with patient outcome. Results from this study further define the role of HKII in colorectal cancer progression and show that 3-bromopyruvate could be useful as an anti-cancer therapy against CRC tumors with high expression of HKII. Citation Format: Nelson Ho, Brenda L. Coomber. Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1180. doi:10.1158/1538-7445.AM2015-1180
Clinical Classification of Myelofibrosis with Myeloid Metaplasia (MMM): Cluster Analysis of 861 Patients Enrolled into a Nationwide Prospective Registry (RIMM).
Authors: M. Marchetti, C. Rognoni, R. Pastorino, R. Bellazzi, P. Magni, S. Quaglini, G. Bergamaschi, R. Invernizzi, U. Magrini, M. Massa, V. Rosti, G. Viarengo, Giovanni Barosi
Journal: Blood (2005)
High dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for HIV-associated lymphoma
Authors: A. Re, C. Cattaneo, M. Michieli, S. Casari, M. Spina, P. Ferremi, M. Mazzuccato, G. Carosi, U. Tirelli, G. Rossi
Journal: Journal of Clinical Oncology (2004)

6506 Background: The introduction of highly active antiretroviral therapy (HAART), has allowed the evaluation of aggressive therapeutic approaches in HIV-associated lymphoma (HIV-Ly). Methods: We report the results of a multiinstitutional program of high dose therapy (HDT) and autologous peripheral blood stem cell (PBSC) transplantation in HAART responsive pts with HIV-Ly refractory or relapsed after standard dose chemotherapy (CT). Pts with active opportunistic infections (OI) or CNS lymphoma were excluded. Results: Twentyfive pts entered the study: 10 HD (five 1st relapse, two 2nd relapse, three refractory) and 15 NHL (eight 1st relapse, one 2nd relapse, two partial remission (PR), four refractory). Median age was 38 (28–56) and CD4 count 207/cmm (17–506). Pts received 2–4 courses of debulking standard dose second-line CT. Five were refractory and died. Adequate PBSC collection was obtained in 17/20 pts (85%) (median CD34+ cells 6.8 x 106/Kg), after cyclophosphamide + G-CSF or G-CSF-supported CT. Two had early disease progression; one is on treatment and 14 received the BEAM regimen and PBSC transplantation with prompt engraftment in all (neutrophils and plt engraftment: 10 (8–10) and 12 days (8–18)). Pts received HAART during the entire program. Treatment-related toxicities (WHO grade 3–4): 3 oral mucositis (3) and 2 hepatic toxicity (3). Infections: 1 Staph. Epidermidis and 1 E. Coli sepsis, 1 Clostridium colitis and 3 FUO. OI: 2 varicella zooster at 3 and 5 mo and 2 esophagus candidosis at 1 and 9 mo. CD4 count decreased after treatment, but a trend toward recovery is seen few mo after transplant. 12/13 evaluable (1 is too early) pts (92%) achieved CR and 1 PR. Relapse occurred in 2 (mo 5 and 12). 11 are alive and 10 disease-free at 9 mo (2–24) after transplant with a projected overall survival (OS) of 64% at 2 ys. The median survival of the entire series (25 pts) from the study entry was 17 mo with a projected OS of 46% at 2 ys (f-up 12 mo (3–42)). Conclusions: Our data confirm on a multiinstitutional basis that HDT and PBSC transplantation is feasible and active as salvage therapy in HIV-Ly in unselected HAART responding patients. No significant financial relationships to disclose.
Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial
Authors: Joseph A. Sparano, Jeannette Y. Lee, Joel Palefsky, David H. Henry, William Wachsman, Lakshmi Rajdev, David Aboulafia, Lee Ratner, Thomas J. Fitzgerald, Lisa Kachnic, Ronald Mitsuyasu
Journal: Journal of Clinical Oncology (2017)

Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus–associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power, 90%), assuming a 35% LRF rate from historical data. Results The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed &lt; 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies.
The Pretreatment Absolute Lymphocyte Count (ALC), but Not the Absolute Monocyte Count (AMC) or ALC/AMC Ratio, Is an Independent Prognostic Factor in Aggressive Non-Hodgkin Lymphoma (aNHL)
Authors: Noridza Rivera-Rodriguez, Fernando Cabanillas, Carlos Montalban, Jose Francisco Tomas, María José Terol, Armando López-Guillermo, Wandaly I. Pardo, Orestes A. Pavia, Margarita Bruno, Karen Janice Santiago, Pablo Guisado-Vasco, Angel Ruedas, Raquel de Oña, Silvia Solorzano, Ana Isabel Teruel, Laura Garcia-Sanchis, Jordina Rovira, Ivan Dlouhy
Journal: Blood (2012)
Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant Recipients
Authors: Seokwoo Park, Eunjeong Kang, Sehoon Park, Yong Chul Kim, Seung Seok Han, Jongwon Ha, Dong Ki Kim, Sejoong Kim, Su-Kil Park, Duck Jong Han, Chun Soo Lim, Yon Su Kim, Jung Pyo Lee, Young Hoon Kim
Journal: Journal of the American Society of Nephrology (2016)

Metabolic acidosis (MA), indicated by low serum total CO 2 (TCO 2 ) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO 2 concentration and clinical outcomes. The prevalence of low TCO 2 concentration (&lt;22 mmol/L) began to increase in KTRs with eGFR&lt;60 ml/min per 1.73 m 2 and ranged from approximately 30% to 70% in KTRs with eGFR&lt;30 ml/min per 1.73 m 2 . Multivariable Cox proportional hazards models revealed that low TCO 2 concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO 2 concentration additionally demonstrated significant associations between low TCO 2 concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO 2 concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.
RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer
Authors: Yajing Liu, Monika L. Burness, Rachel Martin-Trevino, Joey Guy, Shoumin Bai, Ramdane Harouaka, Michael D. Brooks, Li Shang, Alex Fox, Tahra K. Luther, April Davis, Trenton L. Baker, Justin Colacino, Shawn G. Clouthier, Zhi-ming Shao, Max S. Wicha, Suling Liu
Journal: Clinical Cancer Research (2016)

PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)-deficient breast cancers; however, resistance ultimately develops. Furthermore, the benefit of PARP inhibitors (PARPi) in triple-negative breast cancers (TNBC) remains unknown. Recent evidence indicates that in TNBCs, cells that display "cancer stem cell" properties are resistant to conventional treatments, mediate tumor metastasis, and contribute to recurrence. The sensitivity of breast cancer stem cells (CSC) to PARPi is unknown.We determined the sensitivity of breast CSCs to PARP inhibition in BRCA1-mutant and -wild-type TNBC cell lines and tumor xenografts. We also investigated the role of RAD51 in mediating CSC resistance to PARPi in these in vitro and in vivo models.We demonstrated that the CSCs in BRCA1-mutant TNBCs were resistant to PARP inhibition, and that these cells had both elevated RAD51 protein levels and activity. Downregulation of RAD51 by shRNA sensitized CSCs to PARP inhibition and reduced tumor growth. BRCA1-wild-type cells were relatively resistant to PARP inhibition alone, but reduction of RAD51 sensitized both CSC and bulk cells in these tumors to PARPi treatment.Our data suggest that in both BRCA1-mutant and BRCA1-wild-type TNBCs, CSCs are relatively resistant to PARP inhibition. This resistance is mediated by RAD51, suggesting that strategies aimed at targeting RAD51 may increase the therapeutic efficacy of PARPi. Clin Cancer Res; 23(2); 514-22. ©2016 AACR.
Potential of the 5-fluorouracil dose-escalation method for dihydropyrimidine dehydrogenase-deficient patients
Authors: Yoichiro Yoshida, Kenichiro Ogura, Akira Hiratsuka, Naoya Aisu, Yamada Teppei, Kojima Daibo, Syu Tanimura, Kentaro Ogata, Syuji Hara, Yuichi Yamashita
Journal: Annals of Oncology (2015)
Fate of Nonculprit Plaques in Patients With STEMI Undergoing Primary PCI Followed by Statin Therapy
Authors: Daisuke Nakamura, Kunihiro Shimamura, Davide Capodanno, Guilherme F. Attizzani, Massimo Fineschi, Giuseppe Musumeci, Ugo Limbruno, Vasile Sirbu, Micol Coccato, Leonardo De Luca, Hiram G. Bezerra, Francesco Saia, Giulio Guagliumi
Journal: JACC. Cardiovascular imaging (2016)
Study Suggests Alzheimer and Parkinson Disease Are Not Transmitted Through Blood Transfusion
Authors: Jeff Lyon
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study
Authors: Meriem Benmerad, Rémy Slama, Karine Botturi, Johanna Claustre, Antoine Roux, Edouard Sage, Martine Reynaud-Gaubert, Carine Gomez, Romain Kessler, Olivier Brugière, Jean-François Mornex, Sacha Mussot, Marcel Dahan, Véronique Boussaud, Isabelle Danner-Boucher, Claire Dromer, Christiane Knoop, Annick Auffray, Johanna Lepeule, Laure Malherbe, Frederik Meleux, Laurent Nicod, Antoine Magnan, Christophe Pison, Valérie Siroux
Journal: European Respiratory Journal (2016)

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs). The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship. Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (−2.56%, 95% CI −3.86–−1.25 for 5 µg·m −3 of PM 10 ; −0.75%, 95% CI −1.38–−0.12 for 2 µg·m −3 of PM 2.5 and −2.58%, 95% CI −4.63–−0.53 for 10 µg·m −3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 . Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides.
176. An Internally Tagged Methylmalonyl-CoA Mutase (Mut) Displays In Vivo Activity after AAV9 Mediated Gene Delivery
Authors: Jessica Schneller, Julien Senac, Randy Chandler, Charles P. Venditti
Journal: Molecular Therapy (2015)

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder most frequently resulting from mutations in the mitochondrial localized enzyme, methylmalonyl-CoA mutase (MUT). A mouse model replicating the most severe form of MMA in which there is complete loss of Mut expression (Mut-/-) displays neonatal lethality but has been successfully used to demonstrate proof-of-principle for gene therapy using AAV vectors. To model the hepato-, renal and cerebral manifestations of MMA, we have generated several lines of transgenic/knock-out mice to create viable animal models of MMA.
Food Values in Shares and Weights
Journal: JAMA (1942)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Rituximab Infusion Induces NK Activation in Subjects with the High Affinity CD16 Polymorphism.
Authors: George J Weiner, Suresh Veeramani, Siao-Yi Wang, Christopher Dahle, Sue Blackwell, Laura Jacobus, Tina Knutson, Allison C Knutson, Brian J Smith, Brian K Link
Journal: Blood (2009)