tbuckley/cabot-search huggingface dataset:
MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer
Authors: Michael Cohen, Vladimir Scheinker, David Bumcrot, Rebecca Glover, Oskar Rokhlin
Journal: Cancer Research (2008)

1822   Recent reports show that AR is the key determinant for the molecular changes required for resistance to apoptosis and for driving prostate cancer cells from an androgen-dependent to androgen depletion, independent (ADI) state. Further recent publications suggest that downregulation of AR expression should therefore be considered the main strategy for the treatment of ADI disease. However, there is little data about how androgen-dependent cancer cells respond to apoptosis-inducing agents after knocking down AR expression. We therefore investigated whether downregulation of AR expression using siRNA AR (si-AR) would be effective for inducing apoptosis in combination with apoptosis-inducing agents. si-AR prevented apoptosis induced by the DNA damage inducing drugs doxorubicin (DOX) and camptothecin (Campt). These agents activate, i.e. phosphorylate, p53, which in turn regulates the expression of a variety of apoptosis-related genes, including microRNA-34a and 34b/c. We investigated 7 phosphorylation sites of p53 after DOX treatment and found that DOX induced 5 of them (Ser15, 20, 37, 46, and 392); phosphorylation of all 5 sites was inhibited by si-AR. This suggests that at least two kinases are involved in AR-mediated suppression of p53. We have also found that three kinases (SPAK, NFBD1, and CaMKII) are under AR control and participate in events upstream of p53 that result in p53 inhibition. Using q PCR we then investigated miRNA-34a and -34c expression. The level of miRNA-34a increased 3X after DOX treatment but no increase was found in si-AR cells; the level of miRNA-34c increased 27X after DOX and only by 2X with si-AR. The data suggest that AR-dependent inhibition of p53 results in suppression of microRNA-34a and -34c that in turn inhibits DOX-induced apoptosis. To directly investigate the role of microRNA-34 in apoptosis, we transfected cells with anti-microRNA-34 oligonucleotides or with microRNA-34, and found that anti-microRNA-34a/c inhibited DOX-mediated apoptosis whereas microRNA-34a/c enhanced DOX-mediated apoptosis; even without DOX treatment microRNA-34 transfection itself induced caspase activity. Taken together, our data indicate that microRNA-34a and 34c play important roles in AR-dependent p53-mediated apoptosis in prostate cancer.
Prospective, Randomised, Double-Blinded, Placebo-Controlled Trial of Glyceryl Trinitrate Ointment in the Treatment of Early Symptomatic Haemorrhoids
Authors: M Aslam, S Humadi
Journal: Endoscopy (2004)

Haemorrhoids are dilated vascular cushions of the anal canal. Although they are common, their precise aetiology remains unknown and there is no optimum method for treating symptomatic haemorrhoids.
Progress in the synthesis and biological evaluation of lipid A and its derivatives
Authors: Jian Gao, Zhongwu Guo
Journal: Medicinal Research Reviews (2017)

Lipid A is one of the core structures of bacterial lipopolysaccharides (LPSs), and it is mainly responsible for the strong immunostimulatory activities of LPS through interactions with the Toll-like receptors and other molecules in the human immune system. To obtain structurally homogeneous and well-defined lipid As and its derivatives in quantities meaningful for various biological studies and applications, their chemical synthesis has become a focal point. This review has provided a survey of significant progresses made in the synthesis of lipid A, and its derivatives that carry diverse saturated and unsaturated lipids, have the phosphate group at its reducing end replaced with a more stable phosphate or carboxyl group, or lack the reducing end phosphate or both phosphate groups, as well as progresses in the synthesis of LPS analogs and other lipid A conjugates. These synthetic molecules have facilitated the elucidation of the structure-activity relationships of lipid A useful for the design and development of lipid A based therapeutics, such as those utilized to treat sepsis, and other medical applications, for example the use of monophosphoryl lipid A as a carrier molecule for the study of fully synthetic self-adjuvanting conjugate vaccines. These topics are also briefly covered in the current review.
Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS
Authors: Detian Yuan, Shan Huang, Emanuel Berger, Lei Liu, Nina Gross, Florian Heinzmann, Marc Ringelhan, Tracy O. Connor, Mira Stadler, Michael Meister, Julia Weber, Rupert Öllinger, Nicole Simonavicius, Florian Reisinger, Daniel Hartmann, Rüdiger Meyer, Maria Reich, Marco Seehawer, Valentina Leone, Bastian Höchst, Dirk Wohlleber, Simone Jörs, Marco Prinz, Duncan Spalding, Ulrike Protzer, Tom Luedde, Luigi Terracciano, Matthias Matter, Thomas Longerich, Percy Knolle, Thomas Ried, Verena Keitel, Fabian Geisler, Kristian Unger, Einat Cinnamon, Eli Pikarsky, Norbert Hüser, Roger J. Davis, Darjus F. Tschaharganeh, Roland Rad, Achim Weber, Lars Zender, Dirk Haller, Mathias Heikenwalder
Journal: Cancer Cell (2017)
Management of Hereditary Haemochromatosis: A Retrospective Audit at Cork University Hospital
Authors: J McCarthy, O Crosbie, S O'Mahony
Journal: Endoscopy (2004)

Background: Hereditary haemochromatosis (HH) has a high prevalence (1 in 200) in Celtic populations. Guidelines are available for the management of this disorder. However patients are managed by different specialties with varying protocols.
Comparison of five video-assisted intubation devices by novice and expert laryngoscopists for use in the aeromedical evacuation environment
Authors: Matthew C. Wallace, SSgt Tyler Britton, Robbie Meek, Sharon Walsh-Hart, Col Todd E. Carter, Steven J. Lisco
Journal: Military Medical Research (2017)

The critically ill or injured patient undergoing military medical evacuation may require emergent intubation. Intubation may be life-saving, but it carries risks. The novice or infrequent laryngoscopist has a distinct disadvantage because experience is critical for the rapid and safe establishment of a secured airway. This challenge is compounded by the austere environment of the back of an aircraft under blackout conditions. This study determined which of five different video-assisted intubation devices (VAIDs) was best suited for in-flight use by U.S. Air Force Critical Care Air Transport Teams by comparing time to successful intubation between novice and expert laryngoscopists under three conditions, Normal Airway Lights on (NAL), Difficult Airway Lights on (DAL) and Difficult Airway Blackout (DAB), using manikins on a standard military transport stanchion and the floor with a minimal amount of setup time and extraneous light emission.A convenience sample size of 40 participants (24 novices and 16 experts) attempted intubation with each of the 5 different video laryngoscopic devices on high-fidelity airway manikins. Time to tracheal intubation and number of optimization maneuvers used were recorded. Kruskal-Wallis testing determined significant differences between the VAIDs in time to intubation for each particular scenario. Devices with significant differences underwent pair-wise comparison testing using rank-sum analysis to further clarify the difference. Device assembly times, startup times and the amount of light emitted were recorded. Perceived ease of use was surveyed.Novices were fastest with the Pentax AWS in all difficult airway scenarios. Experts recorded the shortest median times consistently using 3 of the 5 devices. The AWS was superior overall in 4 of the 6 scenarios tested. Experts and novices subjectively judged the GlideScope Ranger as easiest to use. The light emitted by all the devices was less than the USAF-issued headlamp.Novices intubated fastest with the Pentax AWS in all difficult airway scenarios. The GlideScope required the shortest setup time, and participants judged this device as the easiest to use. The GlideScope and AWS exhibited the two fastest total setup times. Both devices are suitable for in-flight use by infrequent and seasoned laryngoscopists.
Relationship between EASI and SCORAD severity assessments for atopic dermatitis
Authors: Rishi Chopra, Paras P. Vakharia, Ryan Sacotte, Neha Patel, Supriya Immaneni, Takeshia White, Robert Kantor, Derek Y. Hsu, Jonathan I. Silverberg
Journal: Journal of Allergy and Clinical Immunology (2017)
Impact of weight loss and exercise on VEGF levels in breast cancer survivors.
Authors: Tara Beth Sanft, Brenda Cartmel, Maura Harrigan, Fangyong Li, Erikka Loftfield, Mary Playdon, Yang Zhou, Cary Philip Gross, Jennifer A. Ligibel, KATHRYN H. SCHMITZ, Dawn L. Hershman, Lajos Pusztai, Melinda L Irwin
Journal: Journal of Clinical Oncology (2016)

10103 Background: Obesity and physical inactivity are associated with breast cancer recurrence and mortality. The mechanisms explaining these associations are not fully understood. Vascular Endothelial Growth Factor (VEGF) is an essential component in angiogenesis, common to both tumor vascularization and adipose tissue expansion. VEGF levels have been found to be elevated in the serum of women with breast cancer and associated with a poorer prognosis. This study looked at VEGF changes in breast cancer survivors participating in either a weight loss study or an exercise study. We hypothesized that weight loss would be correlated with decreased VEGF levels compared to exercise alone. Methods: We examined changes in serum VEGF in two randomized trials in overweight breast cancer survivors: a diet-induced weight loss trial of 100 women randomized to a weight loss and exercise counseling intervention with either telephone or in-person counseling (n = 67) or usual care (n = 33), and a supervised exercise trial in which 121 women were randomized to aerobic exercise (n = 61) or usual care (n = 60). Body composition (height, weight, and DEXA scans), physical activity and diet were measured at baseline and 6-months. Fasting blood samples were collected at baseline and 6 months. We compared mean baseline to 6-month between groups using a general linear regression model. Results: In the weight-loss trial, the weight loss group had a 6% weight loss and a 5.0% decrease in VEGF (mean ± 95% CI -16.4 pg/ml ± 9.2) while the usual care group had a 2% weight loss and a 4.8% increase in VEGF (12.5 pg/ml ± 11.7), p = 0.05 between groups. In the exercise trial, no significant weight loss was observed in either group. The change in VEGF from baseline to 6 months did not differ by randomization group. The 6 month change in the exercise group was 1.4 ± 6.8 (0.5% increase) and usual care group was 12.6 ± 7.3 (4.6% increase), p = 0.27 between groups. Conclusions: VEGF decreased in breast cancer survivors randomized to a weight loss intervention but did not change in those participating in an exercise only trial. Weight loss may play a larger role in mediating changes in VEGF compared to exercise alone.
Sarcoidosis and aspergillosis: a tough combination
Authors: David W. Denning
Journal: European Respiratory Journal (2017)

It should have been a wake-up call. Thirty years ago, Tomlinson and Sahn [1] found that seven out of 12 (58%) patients with aspergillosis complicating sarcoidosis died over a 2 year period. Three years earlier, Wollschlager and Khan [2] had found evidence of aspergillosis in 12% of 100 consecutive sarcoidosis referrals, and aspergillomas were found in 53% of the 19 patients with fibrocystic aspergillosis. Yet the literature was almost silent on this topic despite an estimated global prevalence of 1.2 million patients with sarcoidosis [3], until 2008. In that year, Hours et al. [4] surveyed pulmonary cavitary sarcoidosis and its complications in their tertiary care service for sarcoidosis in Paris, France. They found that 3.9% had cavitary lesions and 2.1% an aspergilloma. This team have followed that report up in this issue of the European Respiratory Journal with a detailed study of chronic pulmonary aspergillosis complicating pulmonary sarcoidosis [5]. Others have noted the complexity of this dual pulmonary condition [6]. CPA is a serious complication of sarcoidosis contributing to fibrosis, respiratory failure and haemoptysis <http://ow.ly/cMyQ30bNG4z>
Phase II study of topotecan and cisplatin with sequential radiotherapy in elderly small cell lung cancer patients (Okayama Lung Cancer Study Group; OLCSG 0102).
Authors: Toshio Kubo, Shingo Harita, Toshiaki Okada, Haruhito Kamei, Shinobu Hosokawa, Tadashi Maeda, Toshiyuki Kozuki, Keiichi Fujiwara, Katsuyuki Hotta, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2015)

7572 Background: The standard treatment for elderly patients with localized small cell lung cancer (LD-SCLC) has not been established. The Okayama Lung Cancer Study Group previously performed a phase I trial using low-dose split cisplatin and topotecan (TP) therapy for elderly SCLC patients and determined the recommended dose. Here, we performed a phase II trial using low-dose split TP therapy with sequential thoracic radiotherapy (TRT) for elderly LD-SCLC patients. Methods: Patients aged ≥76 years with untreated LD-SCLC and a performance status of 0–2 were enrolled. Topotecan (1.0 mg/m2, days 1–3) and cisplatin (20 mg/m2, days 1–3) were administered for a maximum of four courses, and sequential TRT (1.8 Gy/day for a total of 45 Gy) was added. The primary endpoint was the overall response rate (ORR). We assumed that an ORR of 0.90 in eligible patients would indicate potential usefulness, whereas an ORR of 0.70 was the lower limit of interest, with α = 0.05 and 1−β = 0.80. Results: A total of 22 cases were registered between 2004 and 2014. Of these, 19 individuals were male, the median age was 79 years, and the median Charlson Comorbidity Index value was 3. The median number of chemotherapy courses was 3, the proportion of patients who could initiate TRT was 63.6%, and the proportion of patients who could complete whole planned treatment was 45.5%. The ORR was 0.68 (15/22 cases; 95% confidence interval, 0.47–0.89), which was below the threshold. The median progression-free survival and overall survival were 9.1 months and 22.2 months, respectively. The observed grade 3–4 toxicities included neutropenia in 95.5% of patients, thrombocytopenia in 50.0%, anemia in 36.0%, and febrile neutropenia in 32.0%. Conclusions: Although low-dose split TP and sequential TRT exerted positive effects on survival, the primary endpoint was not met and severe bone marrow suppression was observed. Therefore, further consideration of the regimen including the timing of TRT is required. Clinical trial information: C000000134.
Abstract 251: Development of a Transgenic Goat Model with Cardiac-Specific Overexpression of Transforming Growth Factor-β1 to Study the Relationship Between Atrial Fibrosis and Atrial Fibrillation
Authors: Irina A Polejaeva, Justin Hall, Qinggang Meng, Xinchang Zhou, Benjamin R Sessions, Kip Panter, Rusty Stott, Heloisa M Rutigliano, Christopher J Davies, Zhongde Wang, Ravi Ranjan, Derek Dosdall, Rob MacLeod, Nassir Marrouche, Kenneth L White
Journal: Circulation Research (2012)

Studies on patients, large animal models and transgenic mouse models have shown a strong association of atrial fibrosis with atrial fibrillation (AF). However, it is unclear whether there is a causal relationship between atrial fibrosis and AF or whether these events appear as a result of independent pathological changes in the heart. We are testing the hypothesis that goats that overexpress TGF-β1 (transforming growth factor beta1) specifically in cardiac myocytes will develop atrial fibrosis that in turn will lead to AF. Many aspects of AF-related remodeling have been studied comprehensively in goat models. However, these AF models are typically mechanically induced (eg, the rapid atrial pacing model). This unique transgenic goat model has the potential to offer insights into the role of fibrosis in AF initiation and progression without the confounding effects of mechanical AF induction. Somatic cell nuclear transfer (SCNT or cloning) was used to produce TGF-β1 transgenic pregnancies. First, pcDNA3.1DV5-MHC-TGF-β1cys33ser vector was constructed by subcloning the MHC-TGF-β1 fragment from the plasmid pUC-BM20-MHC-TGF-β1 into the pcDNA3.1D V5 vector. The NeonTM transfection system was used to electroporate primary goat fetal fibroblasts. After two weeks of G418 selection, the resulting G418 resistant colonies were screened by PCR to confirm transgene integration into goat genomic DNA. PCR positive cells were used for SCNT. Cloned embryos (n=264) were cultured for 12-60 h in vitro and then transferred into synchronized recipient females (n=15). Confirmation of pregnancy was done by ultrasonography on day 30 post-transfer. At the time of this abstract submission, 40% (6/15) of recipients were confirmed to be pregnant as determined by the presence of a heartbeat. The range for the stage of gestation is between day-60 and day-120. The first delivery date is April 28, 2012. Several reports documented no pregnancy losses after 30 days of gestation in goats. Therefore, we expect that most if not all of these pregnancies will result in delivery of live offspring. To our knowledge, this will be the first transgenic goat model generated for cardiovascular research.
Differentiation of Tumour from Normal Colorectal Tissue by SELDI-MS Protein Profiling
Authors: AM Lennon, D Stuart, AC Tan, E Fox, KS Sheahan, JM Hyland, DP O'Donoghue, B Brown
Journal: Endoscopy (2004)

Introduction Surface enhanced laser desorption ionisation mass spectrometry (SELDI-MS) is a technique which has been used to study proteomic patterns in cell lines, tumour material and serum samples but has yet to studied in colorectal cancer tissue specimens. This was a feasibility study to determine if SELDI-MS was able to differentiate tumour from normal colorectal tissue specimens.
Molecular Pathways: Targeting the Microenvironment of Liver Metastases
Authors: Simon Milette, Jason K. Sicklick, Andrew M. Lowy, Pnina Brodt
Journal: Clinical Cancer Research (2017)

Abstract Curative treatment for metastatic solid cancers remains elusive. The liver, which is nourished by a rich blood supply from both the arterial and portal venous systems, is the most common site of visceral metastases, particularly from cancers arising in the gastrointestinal tract, with colorectal cancer being the predominant primary site in Western countries. A mounting body of evidence suggests that the liver microenvironment (LME) provides autocrine and paracrine signals originating from both parenchymal and nonparenchymal cells that collectively create both pre- and prometastatic niches for the development of hepatic metastases. These resident cells and their molecular mediators represent potential therapeutic targets for the prevention and/or treatment of liver metastases (LM). This review summarizes: (i) the current therapeutic options for treating LM, with a particular focus on colorectal cancer LM; (ii) the role of the LME in LM at each of its phases; (iii) potential targets in the LME identified through preclinical and clinical investigations; and (iv) potential therapeutic approaches for targeting elements of the LME before and/or after the onset of LM as the basis for future clinical trials. Clin Cancer Res; 23(21); 6390–9. ©2017 AACR.
Diagnosis and management of the infertile couple: missing information
Journal: Human Reproduction Update (2004)

Missing information about reproductive processes is an important barrier to conception and live birth among infertile couples. In vitro and genetic techniques have been informative, but not enough is known about potential defects in fertilization, implantation and early embryo development to define explicit infertility diagnoses and direct specific treatment. Study of gamete quality is needed because endocrine and ultrasound measurements in the female cannot determine oocyte quality and semen analysis in the male is a limited predictor of fertilizing ability. Also, more study would help in understanding the conditions in the Fallopian tube and elsewhere that foster fertilization and embryo development. Research in related subjects is also needed: after many years of enquiry, there exists little or no evidence to determine how and if endometriosis causes subfertility. In contrast, the recently described impact of smoking in males is large, clinically important and possibly reversible. Missing information limits the choice of specific treatment, puts a ceiling on the overall prognosis, increases the likelihood of persistent infertility and forms a barrier to understanding the broader meanings of success in the management of infertility.
A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality
Authors: Charlotte Hyldgaard, Ole Hilberg, Alma Becic Pedersen, Sinna Pilgaard Ulrichsen, Anders Løkke, Elisabeth Bendstrup, Torkell Ellingsen
Journal: Annals of the Rheumatic Diseases (2017)

To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD.Matched cohort study.The study was conducted in Denmark, using nationwide, prospectively collected data.Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD.Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models.The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index.ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.
Glioma groups classified by IDH and TERT promoter mutations remain stable among primary and recurrent gliomas
Authors: Zhenyu Zhang, Aden Ka-Yin Chan, Xiaojie Ding, Yanxi Li, Ruiqi Zhang, Lingchao Chen, Ying Liu, Yin Wang, Ji Xiong, Ho-Keung Ng, Yu Yao, Liangfu Zhou
Journal: Neuro-Oncology (2017)

Glioma groups classified by IDH and TERT promoter mutations remain stable among