tbuckley/cabot-search huggingface dataset:
Abstract 9294: Spironolactone Reduces Galectin-3 Levels in Mildly Symptomatic Systolic Heart Failure Patients
Authors: Esra Gucuk Ipek, Senay Akin Suljevic, Haydar Demirel, Neslihan Karalok, Yesim Guray
Journal: Circulation (2013)

Background: Galectin-3, is a biomarker believed to reflect cardiac remodeling and fibrosis in patients with heart failure. Spironolactone, has been reported to reduce fibrosis, improve cardiac function and survival in heart failure patients. Whether spironolactone improves remodeling process by altering galectin-3 is unknown. Methods: 14 patients (ejection fraction ≤35, NYHA class II) being treated with guideline base treatments were enrolled to the study. Baseline echocardiographic measurements were noted and serum samples were obtained for galectin-3 levels. After excluding renal failure and hyperkalemia they were prescribed spironolactone, 25 mg daily. Patients were followed during 3 months for side effects. After the third month of follow up, echocardiographic measurements were repeated and serum samples were recollected for galectin-3 levels. Results: The mean age of the patients was 67±11, 64% of the patients were male. Most of the patients (93%) had ischemic cardiomyopathy. Of all, 14% had diabetes, 71% had hypertension. There was no significant change in left atrial diameter, left atrial volume, left ventricular end systolic diameters and myocardial performance indexes. Comparing to baseline measurements, there were significant improvements in left ventricular ejection fraction (30.3±4.6 vs. 31.3±4.5, p=0.04), left ventricular end diastolic diameter (58.9±0.5 vs. 58.2±0.6, p=0.03), left ventricular end diastolic volume (137.2±16.4 vs. 127.8±20.4, p=0.002), left ventricular end systolic volume (95.4±15.3 vs. 88±16.9, p=0.002). Galectin-3 levels decreased significantly after commencing spironolactone treatment (1.49±0.58 vs. 0.98±0.29 p=0.01). Decrease in galectin-3 levels were significantly correlated with the improvements in the left ventricular end diastolic and end systolic volumes (p=0.01 and p=0.02 respectively). Conclusions: Administration of spironolactone to patients with mildly symptomatic heart failure has beneficial effects on left ventricular remodeling and has a correlation with a significant decrease in serum galectin-3 levels. Spironolactone may improve remodeling by altering galectin-3 levels. Larger studies are necessary to evaluate whether these findings have clinical implications.
급성 바이러스성 간염
Authors: 변관수 ( Kwan Soo Byun )
Journal: Clinical and Molecular Hepatology (2010)

The epidemiology of acute viral hepatitis (AVH) is dynamic and influenced by various factors including hygiene, socioeconomic changes and vaccination strategies. Of cases of AVH in Korea, acute hepatitis A accounted for 77%, acute hepatitis B for 4%, acute hepatitis C for 3%. During recent years, acute hepatitis A incidence has increased remarkably up to 14,966 cases in 2009. It suggests that the incidence of hepatitis A might be higher than 30 cases per 100,000 population. This finding urges to promote vaccination for childhood and high risk groups. The incidence of acute hepatitis B has declined dramatically in nearly all countries since 1992 when hepatitis B vaccine be included in all infant immunization programs. Antiviral treatment is only indicated for patients with fulminant hepatitis B and protracted, severe acute hepatitis B. An accurate diagnosis of acute hepatitis C can often be elusive. Patients with acute hepatitis C should be considered for interferon-based antiviral therapy. In recent years, autochthonous hepatitis E has been reported in many non-endemic developed countries. During recent years, in Korea, over a hundred cases of presumed hepatitis E has been reported. The diagnosis in majority of these cases depended on only IgM anti-HEV test, however, serologic test did not correlate completely with viremia in the diagnosis of acute HEV infection. Detection of HEV RNA in sera or feces together with seropositivity for IgM anti-HEV and seroconversion to IgG anti-HEV should be included in the diagnosis for HEV infection.
Development of a Novel Selective Amplifier Gene for Controllable Expansion of Transduced Hematopoietic Cells
Authors: Keiko Ito, Yasuji Ueda, Masaki Kokubun, Masashi Urabe, Toshiya Inaba, Hiroyuki Mano, Hirofumi Hamada, Toshio Kitamura, Hideaki Mizoguchi, Tsuneaki Sakata, Mamoru Hasegawa, Keiya Ozawa
Journal: Blood (1997)
Tubular Epithelial NF-κB Activity Regulates Ischemic AKI
Authors: Lajos Markó, Emilia Vigolo, Christian Hinze, Joon-Keun Park, Giulietta Roël, András Balogh, Mira Choi, Anne Wübken, Jimmi Cording, Ingolf E. Blasig, Friedrich C. Luft, Claus Scheidereit, Kai M. Schmidt-Ott, Ruth Schmidt-Ullrich, Dominik N. Müller
Journal: Journal of the American Society of Nephrology (2016)

NF- κ B is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type–specific functions of NF- κ B in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF- κ B signaling in a mouse model of ischemia-reperfusion injury (IRI)–induced AKI. NF- κ B reporter activity and nuclear localization of phosphorylated NF- κ B subunit p65 analyses in mice revealed that IRI induced widespread NF- κ B activation in renal tubular epithelia and in interstitial cells that peaked 2–3 days after injury. To genetically antagonize tubular epithelial NF- κ B activity, we generated mice expressing the human NF- κ B super-repressor I κ B αΔ N in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF- κ B–dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from I κ B αΔ N-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF- κ B activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.
Economic costs of hepatocellular carcinoma in the United States
Authors: K. Gondek, K. Lang, N. Danchenko, S. Shah, S. Anderson, D. Thompson
Journal: Journal of Clinical Oncology (2008)

6555 Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer in the United States, accounting for 75–80% of all cases. The incidence of HCC increased two-fold between mid-1970s and late-1990s, and in 2002 an estimated 16,210 new cases of primary liver cancer were diagnosed. Currently, HCC patients have limited treatment options and low survival rates. Despite the growing importance of this cancer, data on its economic burden are limited. The objective of this study was to evaluate the annual societal economic burden of HCC in the US. Methods: A prevalence-based modeling approach was used to estimate the aggregate annual societal cost burden of HCC in the US, including healthcare costs and value of lost productivity. Key relationships represented in the model include: (1) the annual number of patients treated for HCC by age group and cancer stage; (2) utilization and unit costs of cancer treatments; (3) work days missed; and (4) annual wage rates. The primary data sources for model estimation were the SEER-Medicare database and the published literature. Results: The annual cost of HCC in the US was estimated to be $437 million per year in the aggregate, or $31,641 per patient. Healthcare costs and lost productivity accounted for 89.2% ($390 million) and 10.8% ($47 million) of the total cost, respectively. The largest component of total cost was inpatient hospitalization, accounting for 37.7% of the total healthcare costs while prescription medications contributed only 0.8% of the total costs. Patients with localized HCC accounted for 43.9% ($171 million) of the total healthcare costs and 49.5% of the total value of lost productivity. Conclusion: The economic burden of HCC is substantial and likely to further increase with increasing incidence of HCC. Interventions to reduce the prevalence of HCC have the potential to yield considerable economic benefits to society. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer
LSC 2012 abstract - Down-regulated let-7b and mir- 126 in tumors and surrounding tissue correlate with high microvessel density and poor survival outcomes in non-small-cell lung cancer patients
Authors: Edin Jusufovic, Matija Rijavec, Dragan Keser, Peter Korosec, Eva Sodja, Ermina Iljazovic, Zorica Radojevic, Mitja Kosnik
Journal: European Respiratory Journal (2012)

32 squamous lung carcinoma, 18 lung adenocarcinoma and 45 healthy individuals were included. let-7b and miR-126 expression were detected by real-time RT-PCR. 3 tissues of lung cancer patients (tumor, tumor surroundings and healthy lung tissue) were compared.  Expression of anti-angiogenic let-7b and miR-126 were significantly lower in tumor tissue and surroundings compared to both healthy lung tissue of diseased patients and control. There was no difference between tumor and tumor surrounding tissue. High let-7b expression and miR-126 expression were highly associated with both better progression-free and overall survival. High micro-vascular density was negatively associated to let-7b and miR-126 expression and highly associated with poor overcome.  Our results confirm a possible role of those two miRNas in lung cancer angiogenesis and suggest the potential new target angiogenic lung cancer therapy.
Clinical Experience with the NCCN Distress Thermometer in Breast Cancer Patients
Authors: Michele Dabrowski, Kenneth Boucher, John H. Ward, Margaret M. Lovell, Angela Sandre, Janet Bloch, Lynne Carlquist, Monica Porter, Larry Norman, Saundra S. Buys
Journal: Journal of the National Comprehensive Cancer Network (2007)

A study was conducted to describe our group's experience using the NCCN Distress Thermometer in an outpatient breast cancer clinic. The NCCN Distress Thermometer was administered to patients attending the breast cancer clinic at Huntsman Cancer Institute during a 4-month period. Effects of disease, treatment, and demographic variables on distress level were analyzed. Patients reporting high distress were contacted by a social worker to determine the cause of the distress. Two hundred and eighty-six (286) subjects completed 403 questionnaires, with 96 patients (34%) reporting high levels of distress (5 or greater on a 10-point scale). No relationship was seen between high distress and stage of disease, type of current treatment, time since diagnosis, age, or other demographic factors. Underlying mental health disorders were associated with a higher level of distress. The Distress Thermometer was a useful method to screen, triage, and prioritize patient interventions. In our experience, the tool promoted communication between the patient and the health care team, which enhanced treating psychosocial and physical symptoms. Methods to optimize the use of this screen are proposed.
Fractionated radioimmunotherapy in NHL with DOTA-conjugated, humanized anti-CD22 IgG, epratuzumab: Results at high cumulative doses of 90Y
Authors: F. Kraeber-Bodere, F. Morschhauser, D. Huglo, M. Petillon, J. Chatal, J. L. Harousseau, H. Horne, N. Teoh, W. A. Wegener, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2008)

8502 Background: A phase I/II, multi-center, dose-escalation trial was undertaken to determine the maximum tolerated dose (MTD) for fractionated radioimmunotherapy with 2 or 3 weekly infusions of 90Y-epratuzumab in B-cell non-Hodgkin’s lymphoma (NHL). Methods: All patients (pts) failed ≥1 prior standard chemotherapies, with <25% bone marrow involvement, platelets >100,000/mm3, and measurable disease by CT with no mass >10 cm. The 90Y dose was escalated separately in 3–6 pt cohorts with or without prior bone marrow transplant (BMT) until 2 occurrences of dose limiting toxicity (DLT). Objective responses (OR) and complete responses (CR/CRu) were evaluated by CT-based International Working Group (IWG) criteria and response durability by Kaplan-Meier (K-M) analysis. Results: The 64 pts (32 M/ 32 F, median age 64) enrolled had 1–7 prior therapies (median 2) with 77% receiving prior rituximab. Therapy was well tolerated, and other than hematological DLT, without treatment-related grade 3–4 adverse events. Escalation stopped at 10 mCi/m2 total dose for 17 pts with prior BMT, but otherwise continued with the highest dose regimens including total doses of 40 mCi/m2 (20 mCi/m2 × 2 wk) and 45 mCi/m2 (15 mCi/m2 x 3 wk). For 58 pts now in the database, OR (CR/CRu) rates increased with total dose [17 pts treated at ≤10 mCi/m2, 41.2% (29.4%); 12 pts at 15–20 mCi/m2, 58.3% (50.0%); 29 pts >20 mCi/m2, 72.4% (55.2%)], occurred for all NHL subtypes [31 follicular lymphoma (FCL) pts, 71.0% (58.1%); 14 mantle cell lymphoma pts, 50.0% (21.4%), 10 diffuse large B-cell lymphoma pts, 30.0% (30.0%); 3 marginal zone lymphoma pts, 100% (100%)], and in pts unresponsive to last therapy [17 pts, 71.4% (53.0%)].For FCL, 18 pts with CR/CRu had durable responses with an estimated median progression free survival now of 16.2 mo., including responses continuing up to 4 years. Preliminary information on the most recent pts (all FCL) indicates that 20 mCi/m2 × 2 wk dosing is particularly effective (11/11 ORs, 10/11 CR/CRu’s). Conclusions: Fractionated radioimmunotherapy with epratuzumab appears feasible and safe for further development, having achieved high response rates at total 90Y doses several- fold beyond the 32-mCi (1200-MBq) limit approved for a single dose of Zevalin. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Immunomedics Immunomedics Immunomedics
Five-year retrospective review of end-of-life care quality metrics in a large, multidisciplinary community oncology practice.
Authors: Angela Kalisiak, Elizabeth Ann Gandara, Susan C Hedlund, Justin K Gress
Journal: Journal of Clinical Oncology (2014)

108 Background: It is increasingly recognized that earlier integration of palliative care for patients with advanced cancers positively impacts both cost and quality of oncology care. Compass Oncology (CO) is a multidisciplinary community oncology practice and a member of The US Oncology Network; 39 medical, gynecologic, and radiation oncologists and 18 advance practice providers serve patients at 6 sites in Oregon and Washington. In 2008, CO prioritized practice improvement in end of life care, identifying metrics for ongoing assessment. Between 2009 and 2014, quality improvement (QI) projects focused on communication skills; whole-staff palliative care education; integration of social workers; initiation of embedded palliative care at 2 sites; and development of a more standardized approach to Advance Care Planning (ACP). Methods: Systematic retrospective record review of patient deaths from January 2009 to December 2013, targeting analysis of hospice utilization, chemotherapy use at end of life, and ACP. Results: Among patients with a CO visit within 6 months of a documented date of death (n= 783 in 2009; n= 909 in 2013), both hospice utilization and ACP participation improved significantly. Percent of patients with evidence for Advance Directive (AD), POLST or code status documented in the electronic medical record (EMR) improved from 36% in 2009 to 50 % in 2013 (p&lt;0.001). Percent of patients enrolled in hospice at the time of death improved from 56% in 2009 to 63% in 2013 (p= 0.003). No statistically significant change was noted in % patients receiving chemotherapy in the last 14 days of life. Conclusions: Focused implementation of end of life care QI strategies in a large multidisciplinary community oncology practice appears to result in both improved hospice utilization and ACP. Chemotherapy usage in the last 14 days of life remains a meaningful target for intervention. Future QI efforts will focus on ongoing, scalable improvement in these metrics. [Table: see text]
Serum selenium and risk of prostate cancer in Japanese men
Authors: M. Nozawa, M. Yoshida, Y. Saito, M. Nakagawa, T. Ozeki, M. Yoshikawa, Y. Aono, H. Uemura
Journal: Journal of Clinical Oncology (2009)

e16166 Background: Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between serum selenium levels and risk of prostate cancer in men who received a prostate biopsy in our hospital. Methods: Our prospective study included 82 patients who received a prostate biopsy based on elevated PSA levels over 4.0ng/ml. Serum from each patient was sampled to determine the selenium level at the time of biopsy. Of these, 47 patients were diagnosed with prostate cancer (case group) and no malignant lesions in the biopsy specimen were detected in the remains, 35 patients (control group). Results: The mean serum selenium levels in the case and control group were 120.4 (SD, 14.4) ng/mL and 118.5 (SD, 16.1) ng/mL, respectively (p = 0.588). Serum selenium levels at biopsy were not associated with risk of prostate cancer diagnosis. In the case group, the mean serum selenium levels in patients diagnosed with 6 or less in Gleason score and 7 or more were 121.0 (SD, 9.9) ng/mL (n = 14) and 120.1 (SD, 16.1) ng/mL (n = 33), respectively (p = 0.851). Serum selenium levels at biopsy were not associated with Gleason score in the case group. An inverse association between serum selenium and PSA levels at biopsy was observed (p = 0.030). No correlation was observed between serum selenium level and age at biopsy. Conclusions: From this study, serum selenium level cannot predict the result of prostate biopsy. The inverse association between serum selenium and PSA levels may suggest that low selenium levels are associated with an increased incidence of prostate cancer. No significant financial relationships to disclose.
Abstract B2-45: Uncovering coordinated regulation of transcription factors by microRNAs using integrated network models
Authors: Sara JC Gosline, Allan M. Gurtan, Courtney K. JnBaptiste, Andrew Bosson, Pamela Milani, Simona Dalin, Bryan Matthews, Yoon Sing Yap, Phillip A. Sharp, Ernest Fraenkel
Journal: Cancer Research (2015)

Abstract MicroRNAs (miRNAs) are small non-coding RNAs that play a significant role in development and cancer but induce only moderate repression of direct messenger RNA (mRNA) targets, suggesting that they coordinate with other modes of cellular regulation to affect cellular phenotype. In this work we exhaustively profile the transcriptional and post-transcriptional regulatory changes between an isogenic pair of murine fibroblast cell lines with and without Dicer, an enzyme required for miRNA processing. Through quantitative analysis of diverse high-throughput datasets collected from both cell lines, we were able to decouple transcriptional from post-transcriptional changes reflected in mRNA expression changes between cells with and without miRNAs. We present three major findings. First, we find that direct miRNA-mRNA interactions have a limited impact on gene expression changes upon Dicer deletion when compared to changes at transcription. We then introduce an integrative graphical network approach to identify specific transcription factors that explain the observed changes in gene expression upon loss of Dicer. Validation of this computational model via transcription factor over-expression reveals a subset of the miRNA-mediated transcriptional program that is activated upon Dicer loss, confirming that transcriptional networks amplify the effects of miRNAs. Lastly, we use this network to examine coordination between transcriptional and post-transcriptional regulation. We identify numerous coherent and in-coherent feed-forward loops, network motifs that have been alluded to but only minimally studied in the context of microRNAs and transcription factors, and find that genes regulated within feed-forward loops by microRNAs and transcription factors exhibit distinct properties in development. In summary, our work illustrates how transcriptional networks amplify the effects of microRNAs. We show coordinated regulation of transcription factors by microRNAs that suggests that most gene expression changes attributed to microRNAs in diseases such as cancer are due to changes in transcription rather than microRNA-mediated degradataion. As such, this work has the potential to reframe future studies of microRNAs in the context of cancer by shifting the focus to understanding the impact of microRNAs on transcription factors. Citation Format: Sara JC Gosline, Allan M. Gurtan, Courtney K. JnBaptiste, Andrew Bosson, Pamela Milani, Simona Dalin, Bryan Matthews, Yoon Sing Yap, Phillip A. Sharp, Ernest Fraenkel. Uncovering coordinated regulation of transcription factors by microRNAs using integrated network models. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-45.
Comparison of regulatory and structural regions of genes of tryptophan metabolism.
Authors: C Yanofsky
Journal: Molecular Biology and Evolution (1984)

The genes of tryptophan biosynthesis are arranged and regulated differently in many microorganisms. Comparison of the transcription regulatory regions of the trp operons of several species of enterobacteria reveals that those sequences and structures believed to be essential for repression and attenuation control are conserved. Examples of divergent and convergent evolutionary change are presented. Rearrangements involving the homologous trpG and pabA genes and their presumed ancestral bi-specific gene are described. Alignment of homologous sequences of trp polypeptides encoded by fused and nonfused genes from various species reveals short connecting amino acid sequences at fusion junctions. These connecting sequences may be relics of gene fusion events and/or they may facilitate the proper folding of neighboring polypeptide domains.