tbuckley/cabot-search huggingface dataset:
Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342
Authors: Roy S. Herbst, Karen Kelly, Kari Chansky, Philip C. Mack, Wilbur A. Franklin, Fred R. Hirsch, James N. Atkins, Shaker R. Dakhil, Kathy S. Albain, Edward S. Kim, Mary Redman, John J. Crowley, David R. Gandara
Journal: Journal of Clinical Oncology (2010)

Purpose Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m 2 ) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m 2 loading dose followed by 250 mg/m 2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. Results Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036). Conclusion Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.
In Vivo Confocal Microscopy 1 Year after Autologous Cultured Limbal Stem Cell Grafts
Authors: Emilio Pedrotti, Mattia Passilongo, Adriano Fasolo, Mario Nubile, Graziella Parisi, Rodolfo Mastropasqua, Sara Ficial, Marina Bertolin, Enzo Di Iorio, Diego Ponzin, Giorgio Marchini
Journal: Ophthalmology (2015)
Hyposmolality stimulates apical membrane Na+/H+ exchange and HCO3– absorption in renal thick ascending limb
Authors: Bruns A. Watts, David W. Good
Journal: Journal of Clinical Investigation (1999)

The regulation of epithelial Na+/H+ exchangers (NHEs) by hyposmolality is poorly understood. In the renal medullary thick ascending limb (MTAL), transepithelial bicarbonate (HCO3–) absorption is mediated by apical membrane Na+/H+ exchange, attributable to NHE3. In the present study we examined the effects of hyposmolality on apical Na+/H+ exchange activity and HCO3– absorption in the MTAL of the rat. In MTAL perfused in vitro with 25 mM HCO3– solutions, decreasing osmolality in the lumen and bath by removal of either mannitol or sodium chloride significantly increased HCO3– absorption. The responses to lumen addition of the inhibitors ethylisopropyl amiloride, amiloride, or HOE 694 are consistent with hyposmotic stimulation of apical NHE3 activity and provide no evidence for a role for apical NHE2 in HCO3– absorption. Hyposmolality increased apical Na+/H+ exchange activity over the pHi range 6.5–7.5 due to an increase in Vmax. Pretreatment with either tyrosine kinase inhibitors or with the tyrosine phosphatase inhibitor molybdate completely blocked stimulation of HCO3– absorption by hyposmolality. These results demonstrate that hyposmolality increases HCO3– absorption in the MTAL through a novel stimulation of apical membrane Na+/H+ exchange and provide the first evidence that NHE3 is regulated by hyposmotic stress. Stimulation of apical Na+/H+ exchange activity in renal cells by a decrease in osmolality may contribute to such pathophysiological processes as urine acidification by diuretics, diuretic resistance, and renal sodium retention in edematous states.
Genetic control of immune responses in vitro. VI. Experimental conditions for the development of helper T-cell activity specific for the terpolymer L-glutamic aicd60-L-alanine30-L-tyrosine10 (GAT) in nonresponder mice.
Authors: J A Kapp, C W Pierce, B Benacerraf
Journal: The Journal of Experimental Medicine (1975)

Mice which are genetic nonresponders to the random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) not only fail to develop GAT-specific antibody responses when stimulated with soluble GAT either in vivo or in vitro, but develop GAT-specific T cells which suppress the GAT-specific plaque-forming cell response of normal nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (MBSA).Thus, both responder and nonresponder mice have T cells which recognize GAT. However, nonresponder mice can develop GAT-specific helper T cells if immunized with GAT bound to MBSA or to macrophages. The relevance of Ir gene-controlled responses is discussed.
Reversible platypnoea and orthodeoxia after surgical removal of an hydatid cyst from the liver
Authors: D. Patakas, G. Pitsiou, D. Philippou, D. Georgopoulos, E. Mavrofridis
Journal: European Respiratory Journal (1999)

A patient with a large hydatid cyst of the liver developed a positionally symptomatic right to left shunting across a patent foramen ovale with both platypnoea and orthodeoxia, despite normal pulmonary arterial pressures and normal pulmonary function tests. When the patient was in the supine position the calculated right to left shunt was 15.1% and 29.5% when seated. The shunt was attributed to the compression of the right atrium and ventricle by the cyst. Surgical evacuation of the cyst relieved the symptoms and the positionally induced shunting.
Comparison of Continuous Positive Airway Pressure and Valsartan in Hypertensive Patients with Sleep Apnea
Authors: Jean-Louis Pépin, Renaud Tamisier, Gilles Barone-Rochette, Sandrine H. Launois, Patrick Lévy, Jean-Philippe Baguet
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Randomized controlled trials (RCTs) have shown that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) reduces blood pressure (BP). CPAP treatment has never been compared with antihypertensive medications in an RCT.To assess the respective efficacy of CPAP and valsartan in reducing BP in hypertensive patients with OSA never treated for either condition.In this 8-week randomized controlled crossover trial, 23 hypertensive patients (office systolic BP/diastolic BP: 155 ± 14/102 ± 11 mm Hg) with OSA (age, 57 ± 8 yr; body mass index, 28 ± 5 kg/m(2); apnea-hypopnea index, 29 ± 18/h) were randomized first to either CPAP or valsartan (160 mg). The second 8-week period consisted of the alternative treatment (crossover) after a 4-week washout period.Office BP and 24-hour BP were measured before and at the end of the two active treatment periods. Twenty-four-hour mean BP was the primary outcome variable. There was an overall significant difference in 24-hour mean BP between treatments: the change in 24-hour mean BP was -2.1 ± 4.9 mm Hg (P < 0.01) with CPAP, and -9.1 ± 7.2 mm Hg with valsartan (P < 0.001), with a difference of -7.0 mm Hg (95% confidence interval, -10.9 to -3.1 mm Hg; P < 0.001). The difference was significant not only during daytime but also during nighttime: the change in nighttime mean BP with CPAP was -1.3 ± 4.6 mm Hg (not significant), and -7.4 ± 8.4 mm Hg with valsartan (P < 0.001), with a difference of -6.1 mm Hg (P < 0.05) (95% confidence interval, -10.8 to -1.4 mm Hg).In an RCT, although the BP decrease was significant with CPAP treatment, valsartan induced a fourfold higher decrease in mean 24-hour BP than CPAP in untreated hypertensive patients with OSA. Clinical trial registered with www.clinicaltrials.gov (NCT00409487).
Efficacy of IP-10 as a biomarker for monitoring tuberculosis therapy
Authors: Ji Young Hong, GyeongSeo Jung, Young Mi Kim, Hye Jon Lee, Sang Nae Cho, Eu Dong Hwang, Young Jae Kim, In Seon Lee, Se Kyu Kim, Joon Chang, Chul Min Ahn, Young Ae Kang
Journal: European Respiratory Journal (2013)

Objective:  The objective of this study was to evaluate serum IP-10 and TB antigen dependent IP-10 secretion as biomarkers for monitoring TB treatment.   Methods:  Thirty-two patients with active tuberculosis were enrolled and the patients were classified into two groups by the presence of cavity or positive sputum culture after two months of anti TB treatment. In this exploratory study, we assessed the changes in serum IP-10, TB antigen dependent IP-10 and IFN-γ response to QFT-GIT antigens at the time of diagnosis and after treatment completion.   Results:  Significant changes between at the time of TB diagnosis and at therapy completion were observed in the serum IP-10( P  P  P =0.180), whereas the proportion of serum IP-10 responders significantly changed( P =0.008). The reversion rate is prominent in low risk group than the moderate/high risk group. The majority of patients didn’t exhibit QFT-GIT reversion.   Conclusions:  Serum IP-10 and IP-10 response to QFT-GIT antigen might be a useful biomarker for monitoring therapy efficacy in patients with active TB. Further studies in larger cohorts are needed to confirm the consistency of this result and identify the appropriate cutoffs.
Contribution of Bcl-2 Phosphorylation to Bak Binding and Drug Resistance
Authors: Haiming Dai, Husheng Ding, X. Wei Meng, Sun-Hee Lee, Paula A. Schneider, Scott H. Kaufmann
Journal: Cancer Research (2013)

Bcl-2 is phosphorylated on Ser(70) after treatment of cells with spindle poisons. On the basis of effects observed in cells overexpressing Bcl-2 S70E or S70A mutants, various studies have concluded that Ser(70) phosphorylation either enhances or diminishes Bcl-2 function. In the present study, the ability of phosphorylated Bcl-2, as well as the S70E and S70A mutants, to bind and neutralize proapoptotic Bcl-2 family members under cell-free conditions and in intact cells was examined in an attempt to resolve this controversy. Surface plasmon resonance indicated that phosphorylated Bcl-2, Bcl-2 S70E, and Bcl-2 S70A exhibit enhanced binding to Bim and Bak compared with unmodified Bcl-2. This enhanced binding reflected a readily detectable conformation change in the loop domain of Bcl-2. Furthermore, Bcl-2 S70E and S70A bound more Bak and Bim than wild-type Bcl-2 in pull-downs and afforded greater protection against several chemotherapeutic agents. Importantly, binding of endogenous Bcl-2 to Bim also increased during mitosis, when Bcl-2 is endogenously phosphorylated, and disruption of this mitotic Bcl-2/Bim binding with navitoclax or ABT-199, like Bcl-2 downregulation, enhanced the cytotoxicity of paclitaxel. Collectively, these results provide not only a mechanistic basis for the enhanced antiapoptotic activity of phosphorylated Bcl-2, but also an explanation for the ability of BH3 mimetics to enhance taxane sensitivity.
Letter by Doraiswamy Regarding Article, “Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study”
Authors: Vijay Arun Doraiswamy
Journal: Circulation (2010)
Postoperative Adjuvant Chemotherapy Use in Patients With Stage II/III Rectal Cancer Treated With Neoadjuvant Therapy: A National Comprehensive Cancer Network Analysis
Authors: Polina Khrizman, Joyce C. Niland, Anna ter Veer, Dana Milne, Kelli Bullard Dunn, William E. Carson, Paul F. Engstrom, Stephen Shibata, John M. Skibber, Martin R. Weiser, Deborah Schrag, Al B. Benson
Journal: Journal of Clinical Oncology (2012)

Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging.The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model.Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status ≥ 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy.Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary.
Epithelial‐mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by <scp>AKT</scp> activation
Authors: K. Barrette, S. Van Kelst, J. Wouters, V. Marasigan, S. Fieuws, P. Agostinis, J. Oord, M. Garmyn
Journal: British Journal of Dermatology (2014)

Journal Article Epithelial‐mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by AKT activation Get access K. Barrette, K. Barrette Laboratory of Dermatology Department of Oncology KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar S. Van Kelst, S. Van Kelst Laboratory of Dermatology Department of Oncology KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar J. Wouters, J. Wouters Translational Cell & Tissue Research Department of Imaging and Pathology KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar V. Marasigan, V. Marasigan Laboratory of Dermatology Department of Oncology KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar S. Fieuws, S. Fieuws I‐Biostat Interuniversity Institute for Biostatistics and Statistical Bioinformatics KU Leuven and Universiteit Hasselt Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar P. Agostinis, P. Agostinis Laboratory of Cell Death Research and Therapy Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar J. van den Oord, J. van den Oord Translational Cell & Tissue Research Department of Imaging and Pathology KU Leuven Leuven Belgium Search for other works by this author on: Oxford Academic Google Scholar M. Garmyn M. Garmyn Laboratory of Dermatology Department of Oncology KU Leuven Leuven Belgium Correspondence Marjan Garmyn. E‐mail: marjan.garmyn@med.kuleuven.be Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 5, 1 November 2014, Pages 1014–1021, https://doi.org/10.1111/bjd.12967 Published: 01 November 2014
Identification and Characterization of <i>Helicobacter pylori</i> Genes Essential for Gastric Colonization
Authors: Holger Kavermann, Brendan P. Burns, Katrin Angermüller, Stefan Odenbreit, Wolfgang Fischer, Klaus Melchers, Rainer Haas
Journal: The Journal of Experimental Medicine (2003)

Helicobacter pylori causes one of the most common, chronic bacterial infections and is a primary cause of severe gastric disorders. To unravel the bacterial factors necessary for the process of gastric colonization and pathogenesis, signature tagged mutagenesis (STM) was adapted to H. pylori. The Mongolian gerbil (Meriones unguiculatus) was used as model system to screen a set of 960 STM mutants. This resulted in 47 H. pylori genes, assigned to 9 different functional categories, representing a set of biological functions absolutely essential for gastric colonization, as verified and quantified for many mutants by competition experiments. Identification of previously known colonization factors, such as the urease and motility functions validated this method, but also novel and several hypothetical genes were found. Interestingly, a secreted collagenase, encoded by hp0169, could be identified and functionally verified as a new essential virulence factor for H. pylori stomach colonization. Furthermore, comB4, encoding a putative ATPase being part of a DNA transformation-associated type IV transport system of H. pylori was found to be absolutely essential for colonization, but natural transformation competence was apparently not the essential function. Thus, this first systematic STM application identified a set of previously unknown H. pylori colonization factors and may help to potentiate the development of novel therapies against gastric Helicobacter infections.
Human T‐cell leukemia virus (HTLV‐I) p24 antibody in New York City blood product recipients
Authors: Janine M. Jason, J. Steven McDougal, Ciril Cabradilla, V. S. Kalyanaraman, Bruce L. Evatt
Journal: American Journal of Hematology (1985)

Human T-cell leukemia virus (HTLV-I) is known to be associated with certain hematologic malignancies, and a related virus, HTLV-III/LAV, might be the cause of AIDS. Some persons with AIDS have had evidence of HTLV-I infection. Unrelated to these findings, it has been suggested that HTLV-I is transmitted via blood products. We therefore evaluated the serologic status to the HTLV-I core antigen p24 of 48 persons with hemophilia (Hem A) receiving factor concentrate therapy (a group at risk for AIDS), 49 persons with beta-thalassemia major (Thal) receiving frozen packed red blood cells therapy (FPRC), 26 patients with sickle cell anemia (SCA) receiving FPRC, and 18 persons not receiving any blood products. All participants were clinically well; only one had a risk factor other than hemophilia for AIDS, and all were from New York City, an area with a high incidence of AIDS. No Hem A or nontransfused persons had serum antibody to HTLV core p24 antigen; three with Thal and one with SCA were antibody-positive. These results were confirmed by both radioimmunoprecipitation and Western blot techniques. Positive serology did not correlate with any immune findings or quantity of blood products used. These data support that HTLV-I is preferentially transmitted through cellular blood products and that it is an infection for which cellular blood product recipients in at least some areas of the United States are at risk. Concentrate products appear free of transmission risk relative to cellular blood products, but we cannot be certain that this safety is absolute. The public health implications of blood product transmission of HTLV-I merit active, long-term investigation.
Rapid Divergence of Microsatellite Abundance Among Species of Drosophila
Authors: C. L. Ross
Journal: Molecular Biology and Evolution (2003)

Among major taxonomic groups, microsatellites exhibit considerable variation in composition and allele length, but they also show considerable conservation within many major groups. This variation may be explained by slow microsatellite evolution so that all species within a group have similar patterns of variation, or by taxon-specific mutational or selective constraints. Unfortunately, comparing microsatellites across species and studies can be problematic because of biases that may exist among different isolation and analysis protocols. We present microsatellite data from five Drosophila species in the Drosophila subgenus: D. arizonae, D. mojavensis, and D. pachea (three cactophilic species), and D. neotestacea and D. recens (two mycophagous species), all isolated at the same time using identical protocols. For each species, we compared the relative abundance of motifs, the distribution of repeat size, and the average number of repeats. Dimers were the most abundant microsatellites for each species. However, we found considerable variation in the relative abundance of motif size classes among species, even between sister taxa. Frequency differences among motifs within size classes for the three cactophilic species, but not the two mycophagous species, are consistent with other studied Drosophila. Frequency distributions of repeat number, as well as mean size, show significant differences among motif size classes but not across species. Sizes of microsatellites in these five species are consistent with D. virilis, another species in the subgenus Drosophila, but they have consistently higher means than in D. melanogaster, in the subgenus Sophophora. These results confirm that many aspects of microsatellite variation evolve quickly but also are subject to taxon-specific constraints. In addition, the nature of microsatellite evolution is dependent on temporal and taxonomic scales, and some variation is conserved across broad taxonomic levels despite relatively high rates of mutation for these loci.
A Mammalian Myocardial Cell-Free System to Study Cell Cycle Reentry in Terminally Differentiated Cardiomyocytes
Authors: Felix B. Engel, Ludger Hauck, M. Cristina Cardoso, Heinrich Leonhardt, Rainer Dietz, Rüdiger von Harsdorf
Journal: Circulation Research (1999)

Cardiomyocytes withdraw from the cell cycle in the early neonatal period, rendering the adult heart incapable to regenerate after injury. In the present study, we report the establishment of a cell-free system to investigate the control of cell cycle reentry in mammalian ventricular cardiomyocyte nuclei and to specifically address the question of whether nuclei from terminally differentiated cardiomyocytes can be stimulated to reenter S phase when incubated with extracts from S-phase cells. Immobilized cardiomyocyte nuclei were incubated with nuclei and cytoplasmic extract of synchronized H9c2 muscle cells or cardiac nonmyocytes. Ongoing DNA synthesis was monitored by biotin-16-dUTP incorporation as well as proliferating cell nuclear antigen expression and localization. Nuclei and cytoplasmic extract from S-phase H9c2 cells but not from H9c2 myotubes induced DNA synthesis in 92% of neonatal cardiomyocyte nuclei. Coincubation in the presence of cycloheximide indicated that de novo translation is required for the reinduction of S phase. Similar results were obtained with adult cardiomyocyte nuclei. When coincubated with both cytoplasmic extract and nuclei or nuclear extracts of S-phase cells, >70% of adult cardiomyocyte nuclei underwent DNA synthesis. In conclusion, these results demonstrate that postmitotic ventricular myocyte nuclei are responsive to stimuli derived from S-phase cells and can thus bypass the cell cycle block. This cell-free system now makes it feasible to analyze the molecular requirements for the release of the cell cycle block and will help to engineer strategies for regenerative growth in cardiac muscle.