tbuckley/cabot-search huggingface dataset:
Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival
Authors: Daniel F. Hayes, Massimo Cristofanilli, G. Thomas Budd, Matthew J. Ellis, Alison Stopeck, M. Craig Miller, Jeri Matera, W. Jeffrey Allard, Gerald V. Doyle, Leon W.W.M. Terstappen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We reported previously that ≥5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated. Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of ≥5 CTCs/7.5 mL at each blood draw. Results: Median PFS times for patients with &amp;lt;5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with ≥5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with &amp;lt;5 CTC from the five blood draw time points was all &amp;gt;18.5 months. For patients with ≥5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different. Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor in hamsters
Authors: Q. Wang, Y. Wang, D. M Hyde, P. J Gotwals, V. E Koteliansky, S. T Ryan, S. N Giri
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Transforming growth factor β (TGF-β) is a key mediator of collagen synthesis in the development of lung fibrosis. It has previously been shown that the administration of TGF-β antibody and TGF-β binding proteoglycan, decorin, reduced bleomycin (BL) induced lung fibrosis in animals. The present study was carried out to investigate whether intratracheal instillation of TGF-β soluble receptor (TR) would minimise the BL induced lung fibrosis in hamsters. <h3>METHODS</h3> The effect of a recombinant TR (TGFβRII) on the lung collagen accumulation was evaluated in a BL hamster model of pulmonary fibrosis. Animals were divided into four groups and intratracheally injected with saline or BL at 6.5 U/4 ml/kg followed by intratracheal instillation of phosphate buffered saline (PBS) or 4 nmol TR in 0.3 ml twice a week. Twenty days after the first intratracheal instillation the hamsters were killed for bronchoalveolar lavage (BAL) fluid, biochemical, and histopathological analyses. <h3>RESULTS</h3> Treatment of hamsters with TR after intratracheal instillation of BL significantly reduced BL induced lung fibrosis as shown by decreases in the lung hydroxyproline level and prolyl hydroxylase activity, although they were still significantly higher than those of the saline control. Histopathological examination showed a considerable decrease in BL induced fibrotic lesions by TR treatment. However, TR did not prevent the BL induced increases in total cells and protein in the BAL fluid. <h3>CONCLUSIONS</h3> These results suggest that TR has antifibrotic potential in vivo and may be useful in the treatment of fibrotic diseases where increased TGF-β is associated with excess collagen accumulation.
A Comprehensive Transcriptomic and Proteomic Analysis of Hydra Head Regeneration
Authors: Hendrik O. Petersen, Stefanie K. Höger, Mario Looso, Tobias Lengfeld, Anne Kuhn, Uwe Warnken, Chiemi Nishimiya-Fujisawa, Martina Schnölzer, Marcus Krüger, Suat Özbek, Oleg Simakov, Thomas W. Holstein
Journal: Molecular Biology and Evolution (2015)

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration.
Estimating Physician Effects on Glycemic Control in the Treatment of Diabetes
Authors: Peter W. Tuerk, Martina Mueller, Leonard E. Egede
Journal: Diabetes Care (2008)

Researchers have only just begun to investigate physician-related effects on medical outcomes. Such research is necessary for developing empirically informed practice guidelines and policy. The primary goal of this study was to investigate whether glucose management in type 2 diabetes varies by randomly assigned physicians over the course of a year in treatment. A second goal of the study was to investigate whether physician-related effects vary across differential patient characteristics. A tertiary goal was to investigate potential patient-level effects on glucose management.
Molecular diagnosis of a familial nonhemolytic hyperbilirubinemia (Gilbert’s syndrome) in healthy subjects
Authors: Jürgen Borlak, Thomas Thum, Olfert Landt, Katharina Erb, Robert Hermann
Journal: Hepatology (2000)

Recent research has shown that congenital nonhemolytic low grade hyperbilirubinemias in patients with Gilbert's syndrome (GS) are linked to mutations in the TATA box upstream of the uridine 5'-diphosphoglucose glucuronosyltransferase (UGT1A1) gene leading to an impaired bilirubin glucuronidation. In routine clinical practice GS patients can, however, only be suspected by exclusion of other causes of hyperbilirubinemia or substantial liver diseases. We developed a new, sensitive, convenient, and economic polymerase chain reaction (PCR) method for the rapid and reliable identification of gene polymorphisms in the TATA box of the UGT1A1 gene using fluorescence resonance energy transfer (FRET). With this procedure the genotype frequency in a cohort of 266 unrelated individuals from Southern Germany was investigated and the allelic distribution for individual genotypes was 43:45:12 for the (TA)(6)TAA:(TA)(6)TAA/(TA)(7)TAA:(TA)(7)TAA alleles, respectively. The homozygous (TA)(7)TAA genotype was strongly associated with suspected Gilbert's patients and its prevalence in our cohort of 266 Southern German individuals was 12.4%. In this cohort total mean serum bilirubin levels ranged from 5 micromol/L (wild-type 6/6 allele) to 57 micromol/L serum total bilirubin (mutant 7/7 homozygous allele). Median (interquartile range) serum total bilirubin levels were 12 (6) and 21 (13) for the homozygous wild-type and mutant allele, respectively. Our assay enables individual guidance for dose adjustment in suspected GS patients undergoing long-term drug therapies, especially if glucuronidation via UGT1A1 is a major metabolic pathway.
Increases of Amphiregulin and Transforming Growth Factor-α in Serum as Predictors of Poor Response to Gefitinib among Patients with Advanced Non–Small Cell Lung Cancers
Authors: Nobuhisa Ishikawa, Yataro Daigo, Atsushi Takano, Masaya Taniwaki, Tatsuya Kato, Satoshi Hayama, Haruyasu Murakami, Yukio Takeshima, Kouki Inai, Hitoshi Nishimura, Eiju Tsuchiya, Nobuoki Kohno, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract Serum levels of amphiregulin and transforming growth factor-α (TGF-α), which were identified previously to be expressed at high levels in non–small cell lung cancer (NSCLC) with poor response to gefitinib, were examined by ELISA using blood samples taken from 50 patients with advanced NSCLCs. Of 14 cases that revealed above the cutoff line for amphiregulin in serum, 12 responded poorly to gefitinib, whereas 18 of the 36 cases showing below the cutoff revealed partial response (PR) or stable disease (SD; P = 0.026). Thirteen of 15 patients who were positive for TGF-α responded poorly to gefitinib, whereas 18 of the 35 patients with negative TGF-α levels turned out to be relatively good responders (P = 0.014). Of 22 patients with positive values for either or both markers, 19 were poor responders. On the other hand, among 28 patients negative for both markers, 17 were classified into the PR or SD groups (P = 0.001). Gefitinib-treated NSCLC patients whose serum amphiregulin or TGF-α was positive showed a poorer tumor-specific survival (P = 0.037 and 0.002, respectively, by univariate analysis) compared with those whose serum amphiregulin or TGF-α concentrations were negative. Multivariate analysis showed an independent association between positivity for TGF-α and shorter survival times among NSCLC patients treated with gefitinib (P = 0.034). Amphiregulin or TGF-α positivity in NSCLC tissues was significantly higher in male, nonadenocarcinomas, and smokers. Our data suggest that the status of amphiregulin and TGF-α in serum can be an important predictor of the resistance to gefitinib among patients with advanced NSCLC.
Lung Homing of Endothelial Progenitor Cells in Humans with Asthma after Allergen Challenge
Authors: Haruki Imaoka, Navneet Punia, Anam Irshad, Sun Ying, Christopher J. Corrigan, Karen Howie, Paul M. O'Byrne, Gail M. Gauvreau, Roma Sehmi
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Increased bronchial vascularity is a feature of asthma that can contribute to airflow obstruction and progressive decline in lung function. Angiogenesis is associated with the lung homing and in situ differentiation of endothelial progenitor cells (EPC) in mouse models of asthma. We have previously shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice attenuated increased bronchial vascularity and development of airway hyperresponsiveness.We investigated the accumulation of EPC and formation of new blood vessels in the lungs of human subjects with asthma after Ag inhalation challenge.Consenting patients with mild atopic asthma (n = 13) with FEV1 ≥ 70%, methacholine PC20 ≤ 16 mg/ml, and a dual response to Ag were recruited. Sputum levels of EPC were determined by multigating flow cytometry, and lung vascularity was enumerated by immunostaining with von Willebrand factor.Sputum levels of EPC were determined by multigating flow cytometry and lung vascularity was enumerated by immunostaining with von Willebrand factor. There was a significant increase in sputum EPC levels 24 hours post Ag but not diluent challenge. Similarly, a significant increase in the number and diameter of blood vessels in lung biopsy tissue 24 hours post Ag was observed. In vitro culture of EPC demonstrated the capacity of these cells to differentiate into mature endothelial cells and form tubelike vessel structures. In sputum supernatants, there was a significant increase in CXCR2 agonists, IL-8, and Gro-α 24 hours post Ag. Only Gro-α stimulated a significant EPC migrational response in vitro.Our data suggest that increased lung homing of EPC may promote bronchial vascularity in allergic asthmatic responses and that the recruitment of these progenitors maybe orchestrated by CXCR2 chemokines.
AMPA Receptor Trafficking and Synaptic Plasticity
Authors: Roberto Malinow, Robert C. Malenka
Journal: Annual Review of Neuroscience (2002)

▪ Abstract Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.
Distribution of natural killer cells and lymphocyte subclasses in Jessner's lymphocytic infiltration of the skin and in cutaneous lesions of discoid and systemic lupus erythematosus
Authors: SATU VILJARANTA, ANNAMARI RANKI, ARJA-LEENA KARINIEMI, P. NIEMINEN, LEIJA JOHANSSON
Journal: British Journal of Dermatology (1987)

We studied the cell infiltrates in biopsies from lymphocytic infiltration of the skin (LIS), with six monoclonal T cell antigen-specific antibodies and compared the reactivity pattern with those in biopsies from discoid and systemic lupus erythematosus skin lesions and allergic contact skin reactions. A newly described antibody (NK9) recognizing natural killer (NK) cells and activated cytotoxic T lymphocytes was included, and the numbers and activity of circulating NK cells was determined. Immunohistochemical staining revealed that the numbers of NK9-positive cells were highest in LIS. The distribution of T lymphocytes (OKTII + ve), helper T cells (OKT4 + ve), suppressor T cells (OKT8 + ve), Langerhans cells (OKT6 + ve) and activated T cells (anti-Tac + ve) in LIS differed from those in DLE,SLE and allergic contact reactions. However, the number of circulating NK cells (large granular lymphocytes) and the NK activity in peripheral blood were normal in LIS. We conclude that in LIS a distinct type of T cell activation occurs; the cause of this remains to be determined.
Psychosomatic Medicine and Otorhinolarγngology
Authors: Ulrich Lamparter, Hans-Ulrich Schmidt
Journal: Psychotherapy and Psychosomatics (1994)

The article gives a clinically oriented survey of psychosomatic aspects in otorhinolaryngology. After a 50-year history of psychosomatic research in this field, the psychosomatic point of view gives a sufficient approach to a lot of diseases in otorhinolaryngology, especially to numerous and frequent diseases of functional origin, but also to problems of coping and psychosocial support. Different indications to psychoanalytic or behavioral psychotherapeutic treatment are discussed.
THE CHANGING FACE OF TUBERCULOSIS
Authors: Robin E. Huebner, Ph.D., M.P.H, Kenneth G. Castro, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Tuberculosis (TB) remains an important public health problem worldwide, resulting in an estimated 8 to 10 million new cases and 2 to 3 million deaths each year. Between 1953 and 1985, the number of TB cases in the US declined by an average of 6% per year. However, since 1985, TB has been increasing in the US. Approximately 64,000 additional cases of the disease have been reported beyond the number expected had the rate of decline observed from 1980 to 1984 continued from 1985 through 1993. Increases in the number of TB cases have been significant in racial and ethnic minorities, in persons born outside the US, and in children less than 15 years of age. Infection with the human immunodeficiency virus (HIV) has also been recognized as a major risk factor for the development of active TB in persons with latent Mycobacterium tuberculosis infection. The unusual radiographic findings and the increased likelihood of extrapulmonary TB in HIV-infected persons make diagnosis of the disease problematic. Lastly, concomitant with the resurgence of TB has been the emergence of drug resistance. All of these factors make successful control of TB in the US difficult.
Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia
Authors: Alejandro Gutierrez, Li Pan, Richard W.J. Groen, Frederic Baleydier, Alex Kentsis, Jason Marineau, Ruta Grebliunaite, Elena Kozakewich, Casie Reed, Francoise Pflumio, Sandrine Poglio, Benjamin Uzan, Paul Clemons, Lynn VerPlank, Frank An, Jason Burbank, Stephanie Norton, Nicola Tolliday, Hanno Steen, Andrew P. Weng, Huipin Yuan, James E. Bradner, Constantine Mitsiades, A. Thomas Look, Jon C. Aster
Journal: Journal of Clinical Investigation (2014)

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, indicating that PP2A mediates the drug’s antileukemic activity. Finally, human T-ALLs treated with perphenazine exhibited suppressed cell growth and dephosphorylation of PP2A targets in vitro and in vivo. Our findings provide a mechanistic explanation for the recurring identification of phenothiazines as a class of drugs with anticancer effects. Furthermore, these data suggest that pharmacologic PP2A activation in T-ALL and other cancers driven by hyperphosphorylated PP2A substrates has therapeutic potential.
Perspective: Cancer Research in the 1980s
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Perspective: Cancer Research in the 1980s Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 3, 7 February 1990, Pages 176–178, https://doi.org/10.1093/jnci/82.3.176 Published: 07 February 1990
Persistence of the asthmatic response in two animal models with exposure to high and low molecular weight agents
Authors: Marta Olle-Monge, Daniel Alvarez-Simón, Susana Gómez-Ollés, Maria-Dolores Untoria, Ferran Morell, Maria-Jesus Cruz, Xavier Munoz
Journal: European Respiratory Journal (2013)

Introduction: Aim: to compare the persistence of bronchial hyperresponsiveness (BHR) and pulmonary inflammation after the end of exposure to soybean (high-molecular-weight agent, HMW) and ammonium persulfate (AP) (low-molecular-weight agent, LMW) in two animal models of asthma.  Methods: In the AP model, BALB/C mice received dermal applications of AP or dimethylsulfoxide on days 1 and 8 and a single intranasal instillation of AP or saline on day 15. In the soybean model, BALB/C mice received intranasal instillation of soy extract or saline on 5 consecutive days for 5 weeks. BHR was assessed using methacholine challenge. Pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL) 1, 4, 8, 24, 48 and 72 hours after the last exposure to the causal agent.  Results: AP-treated mice presented a sustained increase in BHR which lasted four days after intranasal instillation. Conversely, soybean-treated mice showed a peak response four hours after intranasal instillation. There was a significant increase in the percentage of neutrophils within 24 hours of the challenge, reaching a peak eight hours after exposure (42.35%) in the AP model. In the soybean model, the peak was reached four hours after the challenge (58.44%). The percentage of eosinophils was significantly increased in soybean-treated mice (15.76%, 1 hour after challenge) while no eosinophils were found in BAL of AP-treated mice.  Conclusion: With the LMW agent BHR persisted over time, whereas with the HMW agent the inflammatory profile is characterized by an increase in percentage of eosinophils. Neutrophilic inflammation is present in both models of asthma, although it is more persistent in the AP model.
Riposte! TO J.G.P. Williams' challenge.
Authors: E. L. Lloyd
Journal: British Journal of Sports Medicine (1978)

There are at least three reasons for joining an Association of Sport and Medicine.1 The opportunity sport gives to people to practice medicineIn this group are those whose main interest is in the treatment of sports injuries.2 The possibility of applying medical knowledge to the benefit of sport For these people the challenge and interest is to use anatomy, physiology, biochemistry etc. to develop and improve training methods so that ultimately performance can be improved.Unfortunately the use of anabolic steroids developed from this interest.
Expression of Mutant p193 and p53 Permits Cardiomyocyte Cell Cycle Reentry After Myocardial Infarction in Transgenic Mice
Authors: Hidehiro Nakajima, Hisako O. Nakajima, Shih-Chong Tsai, Loren J. Field
Journal: Circulation Research (2004)

Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell–derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell cycle activity in normal and infarcted hearts were examined. Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants in the heart were generated. Transgene expression had no effect on cardiomyocyte cell cycle activity in uninjured adult hearts. In contrast expression of either transgene resulted in a marked induction of cardiomyocyte cell cycle activity at the infarct border zone at 4 weeks after permanent coronary artery occlusion. Expression of the p193 dominant-interfering mutant was also associated with an induction of cardiomyocyte DNA synthesis in the interventricular septa of infarcted hearts. A concomitant and marked reduction in hypertrophic cardiomyocyte growth was observed in the septa of hearts expressing the p193 dominant-interfering transgene, suggesting that cell cycle activation might partially counteract the adverse ventricular remodeling that occurs after infarction. Collectively these data suggest that antagonization of p193 and p53 activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle reentry in the injured adult heart.