tbuckley/cabot-search huggingface dataset:
Kaempferol inhibits VEGF and HIF-1α genes expression through PI-3 kinase/Akt signaling pathway in ovarian cancer cells
Authors: Haitao Luo, Bing-Hua Jiang, Lingzhi Liu, Yi Chen
Journal: Cancer Research (2008)

1758  For effective prevention and treatment of ovarian cancers, the anti-angiogenesis potential of kaempferol and its signal transduction pathway were investigated.  Two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, were treated with kaempferol. Short-term cytotoxicity was assessed by measuring released lactate dehydrogenase (LDH), and long-term inhibition on cell proliferation was determined by a MTS-based assay. The expression of vascular epidermal growth factor (VEGF) gene was analyzed at both transcription level by RT-qPCR and translation level by ELISA. The upstream regulator of VEGF, hypoxia inducible factor 1 (HIF-1), was also examined at both mRNA level by RT-qPCR and protein level by Western Blot. To identify the signaling pathway that mediates HIF-1 regulation, Erk and Akt phosphorylation were also quantitated by ELISA.  No short-term cytotoxicity was observed in OVCAR-3 cells after 6-hour treatment with kaempferol up to 160 μM, and only a mild inhibition ( 0.40) in both cell lines by kaempferol treatment up to 40 μM, though Western Blot showed that HIF-1α protein levels dropped to 69% for A2780/CP70 cells (p
Profiling of immune related adverse events from nivolumab or pembrolizumab monotherapy in advanced non-small cell lung cancer in real world
Authors: M. Aso, S. Sugawara, Y. Toi, J. Sugisaka, H. Ono, K. Tsurumi, K. Suzuki, H. Shimizu, Y. Domeki, T. Aiba, S. Kawana, R. Saito, K. Terayama, Y. Kawashima, A. Nakamura, S. Yamanda, Y. Kimura, Y. Honda
Journal: Annals of Oncology (2018)
Artificial intelligence for aging and longevity research: Recent advances and perspectives
Authors: Alex Zhavoronkov, Polina Mamoshina, Quentin Vanhaelen, Morten Scheibye-Knudsen, Alexey Moskalev, Alex Aliper
Journal: Ageing Research Reviews (2018)

The applications of modern artificial intelligence (AI) algorithms within the field of aging research offer tremendous opportunities. Aging is an almost universal unifying feature possessed by all living organisms, tissues, and cells. Modern deep learning techniques used to develop age predictors offer new possibilities for formerly incompatible dynamic and static data types. AI biomarkers of aging enable a holistic view of biological processes and allow for novel methods for building causal models—extracting the most important features and identifying biological targets and mechanisms. Recent developments in generative adversarial networks (GANs) and reinforcement learning (RL) permit the generation of diverse synthetic molecular and patient data, identification of novel biological targets, and generation of novel molecular compounds with desired properties and geroprotectors. These novel techniques can be combined into a unified, seamless end-to-end biomarker development, target identification, drug discovery and real world evidence pipeline that may help accelerate and improve pharmaceutical research and development practices. Modern AI is therefore expected to contribute to the credibility and prominence of longevity biotechnology in the healthcare and pharmaceutical industry, and to the convergence of countless areas of research.
Ganoderic acids BT-01, a galectin-1 inhibitor, suppresses ovarian cancer growth in humanized mouse xenograft model
Authors: C.-P. Huang, S.-Y. Chen, H.-H. Lai, Y.-H. Lin, C.-T. Su, S.-J. Wu, C.-H. Chang, C.-C. Tsao, Y.-C. Chen, S.-C. Wang, Y.-H. Liu, S.-B. Lin, T.-H. Chen
Journal: Annals of Oncology (2018)
570 The effects of roziglitazone, metformine and diet with exercise in nonalcoholic fatty liver disease
Authors: F. Akyuz, K. Demir, S. Ozdil, N. Aksoy, S. Poturoglu, D. Ibrisim, S. Kaymakoglu, F. Besisik, G. Boztas, Z. Mungan, Y. Cakaloglu, U. Cevikbas, A. Okten
Journal: Journal of Hepatology (2004)
A randomized investigator initiated phase III study comparing low dose gemcitabine to standard dose gemcitabine with platinum in advanced squamous non driver mutated non-small cell lung cancer
Authors: A. Chandrashekharan, V. Patil, V. Noronha, A. Joshi, A. Choughle, S. Punatar, A. Mahajan, A. Janu, N. Purandare, S. Goud, S. More, S. Das, A. Agrawal, A. Rajpurohit, S. Majumdar, S. Khaddar, K. Prabhash
Journal: Annals of Oncology (2018)
PTH-120 In vivo assessment of foods that stimulate intestinal secretions: implications for dietary advice in ileostomy care
Authors: G Major, V Wilkinson-Smith, K Murray, L Ashleigh, C Hoad, L Marciani, P Gowland, R Spiller
Journal: Gut (2017)

Introduction  Plant foods may stimulate intestinal secretion through chemicals designed to deter herbivores such as lactucins in lettuce and rhein in rhubarb. Increased small bowel water increases ileostomy output and may induce diarrhoea in people with an intact bowel. The aim of the study was to investigate the effect of lettuce and rhubarb on intestinal water content.  Method  Design: a three period, three treatment, crossover trial. Population: adults≥18 without bowel disorders. Interventions: 3 meals of 245±3 kcal, taken with 200 mL water. Meals used: 1) 2 slices white bread with 10g butter (10g fat); 2) 300g cooked rhubarb with 60 mL lactose free cream (22.5g fat); 3) 300g Romaine lettuce with 30 mL mayonnaise (23.5g fat). Meals were eaten one week apart to minimise carryover. The order of meals was randomised using a remote, internet based program. Primary outcome: water content of the small bowel (SBWC) using magnetic resonance imaging (MRI). Secondary outcomes: ascending colon water content and T1 relaxation time (T1AC), an MRI constant reflecting water content; visual analogue scales of bloating and satiety (0–100). MRI analysts were blind to the test meal. Scans were taken fasting and 0, 60, 120, 180 min postprandial. Symptoms were scored every 30 min.  Results  15 subjects completed the study between October 2016 - February 2017. 9 were female, 6 male, median age 21(IQR 20,22) and mean body mass index 21.4kg.m-2 (SD ±2.2). Bread induced a fall in SBWC compared to a rise after lettuce and a greater rise after rhubarb, with significant differences in the area under the curve (0–3 hours) of the change from baseline (p  rhubarb > bread, with scores after lettuce and bread still significantly different at 2 hours. Satiety scores were higher immediately after lettuce. Figures show mean±SEM.  Conclusion  MRI allows assessment of both small and large bowel fluids. Lettuce and rhubarb meals increased small bowel water with later effects on the ascending colon on the arrival of meal residue. Rhubarb may also influence T1 in the colonic chyme. These data demonstrate a mechanism by which food can alter stoma output and stool consistency. Future work is needed to identify the active components of these meals.  Disclosure of Interest  None Declared
Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses
Authors: Zhilei Shan, Yanping Li, Geng Zong, Yanjun Guo, Jun Li, JoAnn E Manson, Frank B Hu, Walter C Willett, Eva S Schernhammer, Shilpa N Bhupathiraju
Journal: BMJ (2018)

Abstract Objectives To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint association to rotating night shift work only, to lifestyle only, and to their interaction. Design Prospective cohort study. Setting Nurses’ Health Study (1988-2012) and Nurses’ Health Study II (1991-2013). Participants 143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline. Exposures Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above. Main outcome measures Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire. Results During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction &lt;0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction. Conclusions Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.
Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma
Authors: H.M. Surowy, A.K. Giesen, J. Otte, R. Büttner, D. Falkenstein, H. Friedl, F. Meier, P. Petzsch, T. Wachtmeister, D. Westphal, D. Wieczorek, W. Wruck, J. Adjaye, A. Rütten, S. Redler
Journal: British Journal of Dermatology (2018)

Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA.To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue.Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction.Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001).The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.
Results of nimotuzumab and vinorelbine, radiation, and re-irradiation for diffuse pontine glioma in childhood.
Authors: Maura Massimino, Veronica Biassoni, Rosalba Miceli, Elisabetta Schiavello, Monika Warmuth, Piergiorgio Modena, Michela Casanova, Emilia Pecori, Felice Giangaspero, Manila Antonelli, Francesca Romana Buttarelli, Filippo Spreafico, Bianca Pollo, Andrea Anichini, Marta Podda, Iacopo Sardi, Loris De Cecco, Udo Bode, Ferdinand Bach, Lorenza Gandola
Journal: Journal of Clinical Oncology (2014)

10020 Background: Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas (DIPG). Findings on the role of EGFR signaling in the onset of childhood DIPG has prompted the use of nimotuzumab, an anti-EGFR monoclonal antibody. Assuming a potential synergy with vinorelbine and radiotherapy, a pilot phase 2 protocol launched in 2009 combined nimotuzumab with concomitant radiation and vinorelbine. A protocol amendment in July 2011 introduced re-irradiation at relapse. The primary endpoint for first-line treatment was objective response rate (CR+PR+SD) according to the RECIST. This report concerns the outcome of this whole strategy. Methods: Vinorelbine 20 mg/m2 was administered weekly, with nimotuzumab 150 mg/m2 in the first 12 weeks of treatment; radiotherapy was delivered from weeks 3 to 9, for a total dose of 54 Gy. Then vinorelbine 25 mg/m2and nimotuzumab were given every other week until the tumor progressed or for up to two years. Re-irradiation consisted of 19.8 Gy, fractionated over 11 days. Baseline and latest MRIs were assessed blindly by an outside neuroradiologist. Results: 25 children (mean age 7.4 years) were enrolled from August 2009 (median follow-up 29 months). A response was observed in 24/25 patients (96%). The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. Eleven of 16 locally-relapsing patients were re-irradiated. One-year PFS and OS rates were 30±10% and 76±9%, respectively; 2-year OS was 27±9%; the median OS was 15 months. Conclusions: This strategy generated interesting results and warrants further investigation.
Effectiveness of the Tacrolimus Swish-and-Spit Treatment Regimen in Patients With Geographic Tongue
Authors: David Aung-Din, Michael Heath, Todd Wechter, Abigail Cline, Steven R. Feldman, Joseph L. Jorizzo
Journal: JAMA Dermatology (2018)

This study evaluates the effectiveness of a twice daily tacrolimus swish-and-spit treatment regimen for geographic tongue.
Osimertinib in advanced or metastatic non-small cell lung cancer patients with EGFR T790M mutation after treatment with EGFR-TKI: Interim analysis of China cohort from the single-arm, open-label, international, multi-center real-world ASTRIS study
Authors: Q. Zhou, H. Zhang, L. Jiang, Y. Shi, Y. Chen, J. Yu, C. Zhou, Y. He, Y. Hu, Z.-A. Liang, Y. Pan, W. Zhuo, Y. Song, G. Wu, G. Chen, Y. Lu, Y. Cheng, S. Lu, J. Wang, Y.L. Wu
Journal: Annals of Oncology (2018)
Low molecular weight heparin (lmwh) inhibits tumor growth through the sequestration of angiogenic cytokines
Authors: Cory Mavis, Dale Henry, Shang-Chiung Chen, Shannon Smiley, Michael Wong
Journal: Cancer Research (2008)

1071  BACKGROUND: Anticoagulation by the use of unfractionated or low molecular weight heparins (LMWHs) has been shown to lead to a survival advantage in cancer patients. There is compelling evidence that these are a result of non-coagulation pathways but the mechanism remains unclear. We hypothesize that soluble heparins inhibit angiogenesis by sequestering growth factors such as FGF away from the target cell surface. In this study we also identify the FGF molecular pathways involved in heparin-induced tumor endothelial cell inhibition as well as determination of the in vivo specific tumor inhibition across different LMWHs.  METHODS: A murine cell line constitutively secreting FGF-1, named Clone C, was established by stably transfecting a FGF-1 expression construct into NIH 3T3 cells. Clone C cells were implanted into mice to yield a working in vivo model of a highly angiogenic tumor. MTS Cell Proliferation assay (Promega) was used to characterize cell growth patterns with heparin treatment in vitro. FGF chimeric protein fused to a hemagglutinin peptide tag at the carboxyl-terminus end was conjugated to a biotin antibody. This conjugate was subsequently bound to an avidin coated Crystalplex bead allowing microscopic tracking of the movement of FGF in the presence or absence of heparins. Whole cell lysates were prepared and protein was visualized by Western blotting.  RESULTS: Clone C tumors in vivo growth were significantly inhibited by LMWHs. The control group tumors were grossly angiogenic and well vascularized. In marked contrast, the heparin treated tumors were smaller, pale and possessed only scant peri-tumoral vessels. Immunohistochemistry staining confirms significantly decreased angiogenesis in the LMWH group. No organ hemorrhage was evident on detailed tissue survey. Direct visual evidence of FGF sequestration occur concomitant with a decrease in Tumor Derived Endothelial Cell (TDEC) mitogenesis. LMWHs inhibit FGF-induced TDEC mitogenesis in a concentration and time dependent manner. The end result is a significant inhibition of down stream signaling through the extracellular signal-regulated kinases (ERK).  CONCLUSIONS: LMWHs both strip and sequester FGF from its receptor resulting in a down regulation of receptor activity and tumor endothelial cell mitosis.
Abstract 24057: Induced Pacemaker Spheroids As A Model To Reverse-Engineer The Native Sinoatrial Node
Authors: Sandra I Grijalva, Jung H Sung, Benjamin W Furman, Pengcheng Han, Jun Li, Hee C Cho
Journal: Circulation (2017)

Background: The sinoatrial node (SAN) has intricate architecture, which facilitates the spontaneous action potentials generated from the SAN to pace and drive the neighboring myocardium. We sought to create an engineered SAN that recapitulates the native SAN’s ability to overcome source-sink mismatch. We hypothesized spheroids consisting of induced pacemaker cells (iPM) can pace and drive surrounding quiescent myocardium. Methods: The iPMs were created by singular expression of a transcription factor, TBX18, to neonatal rat ventricular myocytes as we have previously demonstrated. The iPM or GFP-spheroids (control) were created by subjecting the NRVMs to the AggreWell™ plate at 1000 cells/well, and cultured for three days in suspension. Spheroids consisted of 90% NRVM and 10% cardiac fibroblast. Results: iPM-spheroids demonstrated spontaneous pacing at 145±26 bpm compared to 66±1 bpm (p=6.5770E-9) of control, GFP-spheroids. When one iPM-spheroid was surrounded by a monolayer of quiescent NRVMs (iPM:NRVM=1:100), the iPM-spheroids were able to pace and drive the quiescent ventricular myocardium at a capture rate of 48±7%. In contrast, the random activity of control spheroids captured the myocardium at 7±4% (p=0.0078). A monolayer of TBX18 cells (1:4=TBX18:NRVM) failed to pace and drive the neighboring sheet of ventricular myocytes. iPM-spheroids had a 17-fold increase in SAN-specific gap junction, Cx45, transcripts (p=0.0001) and a 2-fold decrease in myocardial gap junction, Cx43 (p=0.0030), compared to GFP-spheroids. The iPM-spheroids have superior viability compared to control GFP-spheroids, 87±1% and 72±5% respectively (p= 0.0463). TUNEL staining confirmed apoptotic fibroblast in the periphery. When cultured for &gt;2 weeks, iPM-spheroids demonstrated small α-sarcomeric actinin positive cells organized as a mesh in the core, similar to the pacemaker cells in the native SAN. Conclusion: iPM-spheroids can pace and drive surrounding quiescent myocardium, overcoming the source-sink mismatch. The iPM-spheroids are viable in long-term and exhibit native SAN-like pacemaker cell organization. These data provide an in vitro platform on which the design principles of native SAN could be tested.
<i>AncestryPainter</i>: A Graphic Program for Displaying Ancestry Composition of Populations and Individuals
Authors: Qidi Feng, Dongsheng Lu, Shuhua Xu
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Ancestry composition of populations and individuals has been extensively investigated in recent years due to advances in the genotyping and sequencing technologies. As the number of populations and individuals used for ancestry inference increases remarkably, say more than 100 populations or 1000 individuals, it is usually challenging to present the ancestry composition in a traditional way using a rectangular graph. To address this issue, we developed a program, AncestryPainter, which can illustrate the ancestry composition of populations and individuals with a rounded and nice-looking graph to save space. Individuals are depicted as length-fixed bars partitioned into colored segments representing different ancestries, and the population of interest can be highlighted as a pie chart in the center of the circle plot. In addition, AncestryPainter can also be applied to display personal ancestry in a way similar to that for displaying population ancestry. AncestryPainter is publicly available at http://www.picb.ac.cn/PGG/resource.php.
Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1–Mediated Metabolic and Epigenetic Changes
Authors: Kazuya Miyagawa, Minyi Shi, Pin-I Chen, Jan K. Hennigs, Zhixin Zhao, Mouer Wang, Caiyun G. Li, Toshie Saito, Shalina Taylor, Silin Sa, Aiqin Cao, Lingli Wang, Michael P. Snyder, Marlene Rabinovitch
Journal: Circulation Research (2019)

Maintaining endothelial cells (EC) as a monolayer in the vessel wall depends on their metabolic state and gene expression profile, features influenced by contact with neighboring cells such as pericytes and smooth muscle cells (SMC). Failure to regenerate a normal EC monolayer in response to injury can result in occlusive neointima formation in diseases such as atherosclerosis and pulmonary arterial hypertension.We investigated the nature and functional importance of contact-dependent communication between SMC and EC to maintain EC integrity.We found that in SMC and EC contact cocultures, BMPR2 (bone morphogenetic protein receptor 2) is required by both cell types to produce collagen IV to activate ILK (integrin-linked kinase). This enzyme directs p-JNK (phospho-c-Jun N-terminal kinase) to the EC membrane, where it stabilizes presenilin1 and releases N1ICD (Notch1 intracellular domain) to promote EC proliferation. This response is necessary for EC regeneration after carotid artery injury. It is deficient in EC-SMC Bmpr2 double heterozygous mice in association with reduced collagen IV production, decreased N1ICD, and attenuated EC proliferation, but can be rescued by targeting N1ICD to EC. Deletion of EC- Notch1 in transgenic mice worsens hypoxia-induced pulmonary hypertension, in association with impaired EC regenerative function associated with loss of precapillary arteries. We further determined that N1ICD maintains EC proliferative capacity by increasing mitochondrial mass and by inducing the phosphofructokinase PFKFB3 (fructose-2,6-bisphosphatase 3). Chromatin immunoprecipitation sequencing analyses showed that PFKFB3 is required for citrate-dependent H3K27 acetylation at enhancer sites of genes regulated by the acetyl transferase p300 and by N1ICD or the N1ICD target MYC and necessary for EC proliferation and homeostasis.Thus, SMC-EC contact is required for activation of Notch1 by BMPR2, to coordinate metabolism with chromatin remodeling of genes that enable EC regeneration, and to maintain monolayer integrity and vascular homeostasis in response to injury.