tbuckley/cabot-search huggingface dataset:
Interferon–microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis
Authors: Yingcheng Yang, Ximeng Lin, Xinyuan Lu, Guijuan Luo, Tao Zeng, Jing Tang, Feng Jiang, Liang Li, Xiuliang Cui, Wentao Huang, Guojun Hou, Xin Chen, Qing Ouyang, Shanhua Tang, Huanlin Sun, Luonan Chen, Frank J Gonzalez, Mengchao Wu, Wenming Cong, Lei Chen, Hongyang Wang
Journal: Gut (2016)

Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance.Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(△hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms.miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-β/Gli and nuclear factor-κB/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(△hep) and Ifnar1(-/-) mice.These findings demonstrate a new protumourigenic axis involving type I IFN-microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis.
Absence of major depressive disorder in female cancer patients.
Authors: S B Lansky, M A List, C A Herrmann, E G Ets-Hokin, T K DasGupta, G D Wilbanks, F R Hendrickson
Journal: Journal of Clinical Oncology (1985)

This investigation evaluated the prevalence of depression in female patients who had cancer in any of five predesignated sites. Five hundred five women aged 17 to 80 (190 with breast cancer, 143 with gynecologic malignancies, 111 with melanoma, 37 with bowel cancer, and 24 with lymphoma) were randomly screened. Assessment included the Hamilton rating scale for depression, the Zung self-rating depression scale, the Karnofsky performance scale, and a 10-cm visual pain analogue line. The results revealed a mean Hamilton of 10.2 (range, 0 to 41; SD, 7.5), a mean Zung score of 35.3 (range, 11 to 68; SD, 9.6), a Karnofsky median score of 80, and a median pain score of 0. Scores on the Zung scale were highly correlated with those of the Hamilton scale (r = .75). Based on cutoff scores accepted as indicating depression (Hamilton greater than or equal to 20 and Zung greater than or equal to 50), patients were depressed. The depressed subgroup was in significantly more pain, experienced greater physical disability, and was more likely to have had prior episodes of depression as compared to the non-depressed women. The two best predictors of current depression were performance status (Karnofsky) and history of depression. No relationship was found between depression and other demographic variables or disease parameters (diagnosis, time since diagnosis, stage or phase of illness, and current treatment). Our findings indicate that the prevalence of major depression in cancer patients is lower than many previous studies have indicated and falls within the range seen in the general population.
Vorinostat (V) In Combination With Bortezomib (B), Doxorubicin (D) and Dexamethasone (D) (VBDD) In Patients With Refractory Or Relapsed Multiple Myeloma: An Interim Phase I/II Analysis
Authors: Martina Kleber, Dagmar Wider, Kristina Keller, Barbara Groß, Heike Reinhardt, Dorothee Jakobs, Mandy-Deborah Moeller, Manuela Burbeck, Milena Pantic, Annette May, Manfred Jung, Ralph Waesch, Monika Engelhardt
Journal: Blood (2013)
Serum glutathione peroxidase 3 as a biomarker of postoperative relapse in patients with lung cancer∗
Authors: In-Jae Oh, Hyun-Ju Cho, Tae-Ok Kim, Chul-Kyu Park, Jung-Hwan Lim, Young-Chul Kim, Ju-Sik Yoon, Sang-Yun Song, Kook-Joo Na, Yoo-Duk Choi, Byung-Chul Ahn, Seung-Won Lee
Journal: Journal of Thoracic Oncology (2016)
Chronic Inhalation Studies in Mice. II. Effects of Long-Term Exposure to 2R1 Cigarette Smoke on (C57BL/Cum × C3H/AnfCum)F&lt;sub&gt;1&lt;/sub&gt; Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: C J Henry, R E Kouri
Journal: JNCI Journal of the National Cancer Institute (1986)

Standardized exposure conditions with Kentucky reference 2R1 cigarettes were used to expose 2,053 (C57BL/Cum x C3H/AnfCum)F1 female mice (nose only) to fresh, whole cigarette smoke. In addition, 1,014 mice were sham-exposed, and 449 mice were held as shelf controls. The protocol entailed exposing mice to smoke (or sham-exposure) on a daily basis, 5 days/week, for 110 weeks and observing remaining mice until death. A large number of animals was used so that the smoke generation and animal-holding systems could be tested and evaluated and yet provide significant numbers of animals for exposure to cigarette smoke for a major portion of their lifetime. Deposition of smoke particulates was estimated to be about 125-200 micrograms total particulate matter/lung/day. The only lung cancers observed were diagnosed as alveolar adenocarcinomas (AAC). A total of 19 of 978 smoke-exposed mice and 7 of 651 sham-exposed mice were observed with AAC. The difference between the smoke-and sham-exposed groups was not statistically significant at P less than or equal to .05, but the data suggested that the tumors occurred with a shorter latency in the smoke-exposed group (P = .10). The data were analyzed by various methods, including analysis of subsets of the population of animals. A significant increase in the incidence of lung cancer was observed in one subset; however, this difference was not found in the population as a whole or as a result of any other analyses. Under these exposure conditions, 2R1 cigarette smoke would seem to have weak carcinogenic activity in mouse lung tissue. Other changes associated with smoke exposure were increased incidence of pigmented alveolar macrophage accumulation, otitis media, and head and neck fibrosarcomas. However, the incidence of nephritis, hematopoietic cancers (e.g., leukemias, lymphosarcomas, and reticulum cell sarcomas), and pulmonary congestion was significantly higher in the sham-exposed animals.
GLIPR1/RTVP-1 tumor suppressor gene expressed by adenovirus vector as neoadjuvant intraprostatic injection for localized high-risk prostate cancer preceding prostatectomy.
Authors: D. Kadmon, G. Sonpavde, R. K. Jain, G. E. Ayala, M. M. Ittmann, S. Kurosaka, K. Edamura, K. Tabata, B. J. Miles, T. C. Thompson
Journal: Journal of Clinical Oncology (2010)

e15026 Background: GLIPR1/RTVP-1 is up-regulated by p53 in prostate cancer (PCa) cells and has preclinical pro-apoptotic, anti- angiogenic, immunostimulatory and metastasis-suppressing activity. A phase I clinical trial was conducted to evaluate the safety and biologic activity of the neoadjuvant intraprostatic injection of GLIPR1/RTVP-1 expressing adenovirus for high-risk localized PCa before radical prostatectomy (RP). Methods: Eligible men had localized PCa (T1-T2c) with Gleason score >7 or PSA > 10 ng/ml, and were candidates for RP. Patients received the adenoviral vector expressing the GLIPR1/RTVP-1 gene by direct injection into both lobes of the prostate under transrectal ultrasound followed 4 weeks later by RP. Six viral particle (vp) dose levels were evaluated: 1010, 5 x1010, 1011, 5 x1011, 1012 and 5 x1012. Results: Nineteen patients were enrolled. The median age was 64 years. Nine men had T1c, 4 had T2a, and 3 had T2b and T2c clinical stage. The baseline pre-biopsy median PSA was 5.1 ng/ml and the median Gleason Score was 7. Symptomatic toxicities included urinary tract infection (n=3; grade 3 in 2 men), flu-like syndrome (n=3), grade 1 fever (n=1), dysuria (n=1) and photophobia (n=1). Asymptomatic laboratory toxicities were grade 1 elevated AST/ALT (n=1) and elevations of PTT (n=3; 2 were transient, 1 prolonged elevation proven to be lupus anticoagulant). Pathologic stage at RP included pT2 (n=12), pT3 (n=6) and pT3N1 (n=1), with focal positive margins in 3 patients. No pathologic complete remission was seen. Cytopathic effect and marked inflammatory infiltrate was seen in 1 patient each, and prostatitis was seen in 2 patients. Flow cytometry analysis of circulating lymphocytes showed stimulation of CD8+ T cells following AdGLIPR1/ RTVP-1 treatment. Tumor tissue and serum biomarker studies are being analyzed and will be presented. Conclusions: The intraprostatic administration of GLIPR1/RTVP-1 tumor suppressor gene expressed by an adenoviral vector was safe in men with localized high-risk PCa preceding RP. Preliminary evidence of biologic anti-tumor, systemic and local activity was observed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progression Therapeutics
Effects of hypothermia during cardiopulmonary bypass and circulatory arrest on sympathetic nerve activity in rabbits
Authors: S. Tokunaga, T. Imaizumi, K. Fukae, A. Nakashima, M. Hisahara, R. Tominaga, A. Takeshita, H. Yasui, K. Tokunaga
Journal: Cardiovascular Research (1996)

Little is known about the effect of hypothermia on neural regulation. We investigated the effects of hypothermia during cardiopulmonary bypass (CPB) on control of renal (RSNA) and lumbar sympathetic nerve activity (LSNA), and plasma catecholamine levels. We directly measured RSNA (n = 14) and LSNA (n = 6) during CPB in anesthetized rabbits. CPB was performed via cannulae in the aortic root for arterial perfusion and the right atrium for venous drainage. Systemic hypothermia was induced by core cooling. RSNA and LSNA were recorded at the nasopharyngeal temperature of 37, 30, 24, and 18 °C and after rewarming up to 37 °C while keeping mean arterial pressure at 70 mmHg by altering perfusion flow. Other variables such as blood gases or electrolytes were kept constant. RSNA at the temperature of 30, 24, and 18 °C significantly decreased by 91, 97, and 95% from control (37 °C), respectively. LSNA decreased by 18, 57, and 89% from control as well. The decreases in RSNA at 30 and 24 °C were greater than those in LSNA (P < 0.05). At 18 °C both RSNA and LSNA nearly disappeared. Circulatory arrest for 20 min during hypothermia at 18 °C caused no increase in RSNA while it increased LSNA. Plasma catecholamine levels at 18 °C were not different from those at 37 °C. Rewarming to 37 °C increased RSNA and LSNA by 321 and 92% from control (37 °C before cooling), respectively (P < 0.01). Hypothermia progressively decreased and rewarming markedly increased sympathetic nerve activity, but the effects of hypothermia on RSNA and LSNA were not uniform.
Predicting Outcomes in Individual Patients After Transcatheter Aortic Valve Replacement
Authors: Laura Mauri, Patrick T. O’Gara
Journal: JAMA Cardiology (2016)

Fred H. Edwards, MD; David J. Cohen, MD; Sean M. O’Brien, PhD; Eric D. Peterson, MD, MPH; Michael J. Mack, MD; David M. Shahian, MD; Frederick L. Grover, MD; E. Murat Tuzcu, MD; Vinod H. Thourani, MD; John Carroll, MD; J. Matthew Brennan, MD, MPH; Ralph G. Brindis, MD, MPH; John Rumsfeld, MD, PhD; David R. Holmes Jr, MD; for the Steering Committee of the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry
Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade
Authors: Yu Zhao, Hang Li, Yingyi Zhang, Leilei Li, Runping Fang, Yinghui Li, Qian Liu, Weiying Zhang, Liyan Qiu, Fabao Liu, Xiaodong Zhang, Lihong Ye
Journal: Cancer Research (2016)

Abnormal lipid metabolism is a hallmark of tumorigenesis. Accumulating evidence demonstrates that fatty acid synthase (FAS, FASN) is a metabolic oncogene that supports the growth and survival of tumor cells and is highly expressed in many cancers. Here, we report that the oncoprotein, hepatitis B X-interacting protein (HBXIP, LAMTOR5) contributes to abnormal lipid metabolism. We show that high expression of HBXIP in 236 breast cancer patients was significantly associated with decreased overall survival and progression-free survival. Interestingly, the expression of HBXIP was positively related to that of FAS in clinical breast cancer tissues, and HBXIP overexpression in breast cancer cells resulted in FAS upregulation. Mechanistically, HBXIP upregulated SREBP-1c (SREBF1), which activates the transcription of FAS, by directly interacting with and coactivating nuclear receptor (NR) liver X receptors (LXR). Physiologically, LXRs are activated via a coactivator containing NR motif in a ligand-dependent manner. However, in breast cancer cells, HBXIP containing the corepressor/nuclear receptor motif with special flanking sequence could coactivate LXRs independent of ligand. Moreover, overexpressed SREBP-1c was able to activate the transcription of HBXIP, forming a positive-feedback loop. Functionally, HBXIP enhanced lipogenesis, resulting in the growth of breast cancer cells in vitro and in vivo Thus, we conclude that the oncoprotein HBXIP contributes to the abnormal lipid metabolism in breast cancer through LXRs/SREBP-1c/FAS signaling, providing new insights into the mechanisms by which cancer cells reprogram lipid metabolism in their favor. Cancer Res; 76(16); 4696-707. ©2016 AACR.
Molecular evolution of a multigene family in group A streptococci.
Authors: S K Hollingshead, J Arnold, T L Readdy, D E Bessen
Journal: Molecular Biology and Evolution (1994)

The emm genes are members of a gene family in group A streptococci (GAS) that encode for antiphagocytic cell-surface proteins and/or immunoglobulin-binding proteins. Previously sequenced genes in this family have been named "emm," "fcrA," "enn," "arp," "protH," and "mrp"; herein they will be referred to as the "emm gene family." The genes in the emm family are located in a cluster occupying 3-6 kb between the genes mry and scpA on the chromosome of Streptococcus pyogenes. Most GAS strains contain one to three tandemly arranged copies of emm-family genes in the cluster, but the alleles within the cluster vary among different strains. Phylogenetic analysis of the conserved sequences at the 3' end of these genes differentiates all known members of this family into four evolutionarily distinct emm subfamilies. As a starting point to analyze how the different subfamilies are related evolutionarily, the structure of the emm chromosomal region was mapped in a number of diverse GAS strains by using subfamily-specific primers in the polymerase chain reaction. Nine distinct chromosomal patterns of the genes in the emm gene cluster were found. These nine chromosomal patterns support a model for the evolution of the emm gene family in which gene duplication followed by sequence divergence resulted in the generation of four major-gene subfamilies in this locus.
Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation
Authors: Ana Carolina P. Souza, Alexander V. Bocharov, Irina N. Baranova, Tatyana G. Vishnyakova, Yuning G. Huang, Kenneth J. Wilkins, Xuzhen Hu, Jonathan M. Street, Alejandro Alvarez-Prats, Adam E. Mullick, Amy P. Patterson, Alan T. Remaley, Thomas L. Eggerman, Peter S.T. Yuen, Robert A. Star
Journal: Kidney International (2016)
Chemotherapy-induced cardiotoxicity: An animal model
Authors: C. Romano, A. Marinelli, F. Fortunato, L. Adinolfi, G. Salvatore, R. Ciarcia, F. Russo, G. Cuda, S. De Placido, A. R. Bianco
Journal: Journal of Clinical Oncology (2004)

9673 Background:Cardiac side effects of several antineoplastic drugs are dose-limiting and dose-dependent, thus they are a limitation to the optimal delivery of dose-intensive chemotherapy. Aim of present study was to construct a model to evaluate cardiac damage after chemotherapy. Methods: 45 male Sprague-Dawley rats, about 7 weeks old and weighing 200–225 g were divided into two groups: one group of 30 rats, each animal receiving 5Fluoruracil, 20 mg/kg/wk by intraperitoneal injection, Epirubicin, 3 mg/kg/wk by intravenous injection, Cyclophosphamide, 20 mg/kg/wk by intraperitoneal injection once weekly for 3 consecutive weeks (FEC group) and a second group of 15 rats receiving no drugs (Control group). Observation for mortality and clinical signs was carried out daily, body weight and blood pressure were recorded basally, before each drug administration and weekly until sacrifice. 15 animals, 10 in the FEC group and 5 in the control group, were sacrificed at weeks 3, 5 and 6 after the end of treatment. Post-mortem examination, performed on all animals, included a complete gross examination, absolute and relative weights of the heart, ventricular height on long and short axis, interventricular septal dimension, left ventricular diastolic diameter, and microscopic evaluation. The latter included immunochemistry by the use of a monoclonal antibody against the cytoskeleton protein α-Actin, actin-myosin in vitro motility assay, expressed in μm/sec and actin-activated ATPase activity, expressed as μmol/Pi/min/mg of myosin. Results: Cardiac evaluation showed cytoskeleton damage with a significant reduction of α-Actin, of rate of actin sliding myosin-coated surface and actin-activated ATPase activity in cardiac tissue of FEC-treated rats as compared with controls. Such a difference between the two groups increased from week 1 to week 4 from the end of therapy. Conclusions: in this model morphologic changes induced by FEC chemotherapy are associated with biochemical changes. The model could be used to monitor the development and progression of the chemotherapy-induced cardiotoxicity in man. (supported by MURST grant L488) No significant financial relationships to disclose.
Exploring the implications of distinct mutational signatures and mutation rates in aging and cancer
Authors: Edward J. Fox, Jesse J. Salk, Lawrence A. Loeb
Journal: Genome Medicine (2016)

Signatures of mutagenesis provide a powerful tool for dissecting the role of somatic mutations in both normal and pathological processes. Significantly, cancer genomes are dominated by mutation signatures distinct from those that accumulate in normal tissues with age, with potentially important translational implications.
Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity
Authors: Christian Krapp, Dominik Hotter, Ali Gawanbacht, Paul J. McLaren, Silvia F. Kluge, Christina M. Stürzel, Katharina Mack, Elisabeth Reith, Susanne Engelhart, Angela Ciuffi, Veit Hornung, Daniel Sauter, Amalio Telenti, Frank Kirchhoff
Journal: Cell Host & Microbe (2016)
Predictors of mortality in patients treated with non-invasive ventilation for acute hypercapnic respiratory failure due to COPD
Authors: Helmy Haja Mydin, Stephen Murphy
Journal: European Respiratory Journal (2011)

Background: Mortality in patients treated with non-invasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) during an acute exacerbation of COPD (AECOPD) is high. For many patients, AHRF is an end-stage process and NIV may be inappropriate. However there is no definitive method of identifying patients who are unlikely to survive.

Aim: The aim of study was to identify clinical and laboratory variables predictive of mortality in patients treated with NIV for AHRF due to COPD.

Methods: Patients treated with NIV for AHRF due to COPD between 12/09 and 07/10 were included in prospective study. Variables included FEV1, pre-admission treatment, performance status (WHO-PS), clinical observations & composite physiological score (early warning score EWS), routine haematology & biochemistry, and arterial blood gases prior to commencing NIV.

Results: N=65 (29M, 36F); mean (SD) age 71 (10.5) yrs. Mortality was 33.8%. On univariate analysis variables associated with mortality were: WHO-PS ≥3 OR 37.78 (7.41-192.53) p<0.0001; long-term oxygen therapy OR 2.99 (1.03-8.66) p<0.05; anaemia OR 5.54 (1.81-16.92) p<0.003, diastolic blood pressure OR 0.96 (0.92-0.99) p<0.03, raised EWS OR 1.45 (1.06-1.99) p<0.03, severe acidosis (ph<7.20) OR 3.65 (1.17-11.37) p<0.03. On multivariate analysis only anaemia OR 5.86 (1.28-26.87) p<0.03 and WHO-PS ≥3 OR 39.08 (6.83-223.61) p<0.0001 were significant. The presence of both predicted 68% of deaths with a specificity of 94%.

Conclusion: The presence of anaemia and WHO-PS ≥3 are predictive of mortality in patients on NIV for AECOPD. This should prompt the physician to consider the suitability of NIV as a treatment option.
A retinoid X receptor (RXR)-selective agonist bexarotene produces synergistic growth inhibitory activity with gefitinib in non-small-cell lung cancer (NSCLC) cell lines
Authors: B. Fan, A. Negro-Vilar, W. W. Lamph, R. P. Bissonnette
Journal: Journal of Clinical Oncology (2004)

7157 Background: Gefitinib (Iressa) is an orally active epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Bexarotene (Targretin) is a selective RXR agonist approved for the treatment of CTCL, and with clinical activity enhancing survival and delaying progression in NSCLC patients. Our previously published data (Cancer Res. 2001) has shown that bexarotene can suppress the growth of epithelial tumors by modulating the expression and function of EGFR and its ligand, TGFα. Methods: The expression of EGFR, Her-2, EGF, and TGFα were evaluated in a panel of 10 NSCLC cell lines, representing different histomorphologies. Cells were treated with bexarotene either alone or in combination with Iressa and growth and viability were examined. Combination treatments were either concomitant or sequential. Results: Exposure of NSCLC cell lines to bexarotene as a single agent had modest growth inhibitory effects (at > 1 μM). However, exposure of several NSCLC lines to bexarotene (1–3 μM) produced significant decreases in the expression of EGFR, Her-2 and TGFα mRNA and protein. EGF levels were also decreased to a much lesser degree. Bexarotene combined with Iressa produced an enhanced growth inhibitory activity (a left-ward shift of 3–5 fold in the IC50) when compared to Iressa alone. Analysis of the growth inhibition of the bexarotene /gefitinib combination demonstrated a synergistic (CI<1) concentration-dependent growth inhibition in several of the NSCLC cell lines. The extent of synergy between bexarotene and gefitinib was greater at modest drug effect (≤IC50). Conclusions: These results suggest that bexarotene can inhibit the expression of several components of the EGFR-Her-2 signaling pathways, and can cooperate with EGFR-targeted agents to decrease proliferation of NSCLC cells in vitro. These data support the clinical observation, also presented at this meeting (Dragnev, K. et al) suggesting that Targretin has beneficial effects when used with EGFR-TKIs in advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals Ligand Pharmaceuticals
LOCAL Allergic Rhinitis: Entopy or Spontaneous Response?
Authors: Matteo Gelardi, Antonio Guglielmi, Lucia Iannuzzi, Vitaliano Quaranta, Nicola Quaranta, Francesco Marcucci, Massimo Landi, Mario Correale, Annamaria Sonnante, Margherita Rossini, Maria Addolorata Mariggiò, Giorgio Walter Canonica, Giovanni Passalacqua
Journal: Journal of Allergy and Clinical Immunology (2016)