tbuckley/cabot-search huggingface dataset:
Abstract 286: ATPase Inhibitory Factor 1 Regulates Glycolysis in Cardiomyocytes
Authors: Bo Zhou, Yanhua Qiu, Stephen C Kolwicz, Rong Tian
Journal: Circulation Research (2017)

It is known that pathological cardiac hypertrophy is associated with decreased fatty acid oxidation (FAO) and increased reliance on glycolysis. This metabolic remodeling is generally recognized and considered ultimately maladaptive for sustaining myocardial energetics and function. The mechanisms responsible for the switch are poorly understood but appear to be coupled with impaired mitochondrial function. We found that mitochondrial ATPase inhibitor factor 1 (ATPIF1) was up-regulated (by 4-fold, p=0.01) in the failing heart induced by TAC surgery as well as in hypertrophied adult rat cardiomyocytes (CMs) induced by 10 uM phenylephrine (PE, by 3-fold, p=0.01), but not in the physiological hypertrophied heart (p=0.9). ATPIF1 is an inhibitor of ATPase in the mitochondrial ATP synthase, or Complex V. It was shown that upregulation of ATPIF1 increased glycolysis in non-cardiomyocytes. Here we wish to test the hypothesis that ATPIF1 stimulates glycolysis in the heart undergoing pathological hypertrophy. Overexpress ATPIF1 (OE) by adenovirus vector in CMs, which mimics the up-regulation of ATPIF1 induced by PE, increased glycolysis in CMs (control: 8.54±0.61 mpH/min, OE: 11.46±0.48 mpH/min; p=0.006), while ATPIF1 knockdown (KD) by shRNA in PE treated CMs abolished the upregulation of glycolytic capacity (control: 29.27±1.31 mpH/min, KD: 28.61±1.81 mpH/min, control-PE: 40.12±1.33 mpH/min, KD-PE: 32.51±2.09 mpH/min; p=0.003). ATPIF1OE or pathological hypertrophy induced by PE increased the expression of glycolytic enzymes, e.g. GAPDH, GLUT1, LDHA and PKM2, which were abolished by ATPIF1KD. We also found that elevation of ATPIF1 decreased mitochondrial oxygen consumption rate (OCR) and promoted mitochondrial reactive oxygen species (mtROS) production, while the generation of mtROS caused by PE was abrogated in the ATPIF1 deficient CMs. Blockade of mtROS production by expressing mitochondria localized catalase suppressed the increased glycolysis in ATPIF1-OE CMs. In conclusion, our results identify ATPIF1 as a regulator of glycolysis in pathological cardiac hypertrophy, which may provide a mechanism for the regulation of glycolysis through mitochondrial bioenergetics.
Loss of Pdcd4 expression marks adenoma-carcinoma transition and is an independent prognostic factor in colorectal cancer.
Authors: Mudduluru Giridhar, Medved Fabian, Grobholz Rainer, Jost Camela, Gruber Annette, Leupold Joerg H, Heidrich Barbel, Post Stefan, Jansen Aaron, Colburn Nancy H, Allgayer Heike
Journal: Cancer Research (2007)

5455    Purpose:  Tumor suppressor Pdcd4 has been described as an inhibitor of malignant transformation, and first studies suggest a regulation of Pdcd4 by Akt. However, this has not yet been supported by data on patient tissue, and the diagnostic and prognostic potential of Pdcd4 has rarely been studied so far. The present study was performed 1. to determine as to whether Pdcd4 may serve as a diagnostic marker in the adenoma-carcinoma-sequence, 2. to support pAkt-mediated regulation of Pdcd4 in vivo, 3. to obtain first evidence for a prognostic relevance of Pdcd4 expression patterns in colorectal cancer.   Patients and Methods:  Tumors/normal tissues of prospectively followed 71 colorectal cancer patients (median time of follow-up 36 months), and 42 benign adenomas were analyzed for Pdcd4, Akt and pAkt by immunohistochemistry/Western blotting.   Results:  A significant reduction of Pdcd4 protein was observed between normal mucosa and adenomas, and adenomas and tumor tissue (p   Conclusion:  This is the first study to demonstrate an independent impact on clinical prognosis of Pdcd4 in colorectal cancer. Also, data support a regulation of Pdcd4 localization by pAkt in vivo. Furthermore, we suggest Pdcd4 immunohistochemistry as a diagnostic tool for determining the transition between normal, adenoma and tumor tissue.
Abstract #1674: BIM-46187: an inhibitor of the heterotrimeric G-protein complex reduces paclitaxel-induced neuropathy pain
Authors: Christine Favre-Guilmard, Hamida Zeroual-Hider, Chantal Soulard, Caroline Touvay, Sylvia Julien, Pierre-Etienne Chabrier, Florence Meyer-Losic, Gregoire Prevost, Michel Auguet
Journal: Cancer Research (2009)

One of the main dose-limiting toxicity of taxanes is the apparition of peripheral neurotoxicity that can lead the interruption of the treatment. BIM-46187 is an inhibitor of the heterotrimeric G-protein complex signalling through a direct binding to the G-protein subunit alpha. BIM-46187 has the particularity of displaying both antitumor activities (Prevost et al, AACR2008) and anti-hyperalgesic effects (Favre-Guilmard et al, EJP, 2008). Here, we have assessed these antalgic properties of BIM-46187 in a rat model of peripheral neuropathy induced by repeated intraperitoneal injections of paclitaxel (2mg/kg on days 0, 2, 4 and 7). As, paclitaxel induced a bilateral neuropathy, mechanical hyperalgesia was assessed by the mean withdrawal responses of the two hind paws. Hyperalgesia was measured before (day 0) and after (16 days) the first injection of paclitaxel. Measurements were performed prior to treatment and 0.5h, 2.5h and 4h after drug administrations. Acute intravenous injection of BIM-46187 (3mg/kg) significantly reduced the paclitaxel induced neuropathic pain in rats. Its efficacy, potency and duration of action are comparable or better with morphine (3mg/kg, ip). It is noteworthy that in these conditions, unlike morphine, BIM-46187 was not sedative as shown by the lack of effect on the rat motor performance in the rotard test. In addition, BIM-46187 did not modify the intestinal transit as observed with the morphine. In conclusion, this work supports further investigations for the use of BIM-46187 in pain management and more precisely in cancer pain.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1674.
Stopping Leukemia in Its Tracks: Should Preemptive Hematopoietic Stem-Cell Transplantation be Offered to Patients at Increased Genetic Risk for Acute Myeloid Leukemia?
Authors: Kayla V. Hamilton, Luke Maese, Jonathan M. Marron, Michael A. Pulsipher, Christopher C. Porter, Kim E. Nichols
Journal: Journal of Clinical Oncology (2019)
Clinical and Biological Characterisation of Localised High-risk Prostate Cancer: Results of a Randomised Preoperative Study of a Luteinising Hormone-releasing Hormone Agonist with or Without Abiraterone Acetate plus Prednisone
Authors: Eleni Efstathiou, John W. Davis, Louis Pisters, Weimin Li, Sijin Wen, Ryan P. McMullin, Michael Gormley, Deborah Ricci, Mark Titus, Anh Hoang, Amado J. Zurita, NamPhuong Tran, Weimin Peng, Thian Kheoh, Arturo Molina, Patricia Troncoso, Christopher J. Logothetis
Journal: European Urology (2019)
FRI0192 Lipid profile in patients with systemic sclerosis
Authors: J Gozdzik, PJ Kotyla, EJ Kucharz, L Brzezinska-Wcislo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic sclerosis (SSc) is an inflammatory connective tissue disorder characterised by collagen proliferation, vascular damage and internal organ involvement. It is speculated that vascular changes in SSc patients may be at least partially secondary to impaired lipid metabolism. Hypothyroidism has been reported in patients with SSc and thyroid involvement may additionally effect lipid metabolism. <h3>Objectives</h3> The aim of the present study was to evaluate the serum lipid profile in patients with SSc with regard to their thyreometabolic state. <h3>Methods</h3> The group of 49 patients with SSc. (2 man and 47 woman) aged from 18 to 68 yrs (mean 48.16 ± 15,8 yrs) was investigated. Patient group with SSc comprised 13 patients with hypothyroidism and 36 patients with normal thyroid function. Nineteen volunteers (6 men and 13 women) were studied as a controls. Fasting serum total cholesterol, HDL and triglyceride levels as well as thyroid hormones were determined. <h3>Results</h3> Increased cholesterol level was shown in patients with SSc. A significantly increased plasma triglyceride concentration and lower HDL level was found in hypothyroid SSc patients as compared to the SSc patients in euthyroid state. There was no differences in total cholesterol level between hypothyroid and euthyroid group of patients with SSC. <h3>Conclusion</h3> There is no correlation between hypercholesterolemia and thyreometabolic state in patients with SSc Increased triglyceride level is secondary to impaired thyroid function in patients with SScc
Expression and prognostic influence of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer
Authors: G. Cox, J.L. Jones, K.J. O'Byrne
Journal: Thorax (1999)

Background

Matrix metalloproteinases (MMPs) are a family of endopeptidases that digest the extracellular matrix (ECM). Overexpression of different MMPs has been shown to promote tumour cell invasion in vitro. Tissue inhibitors of matrix metalloproteinases (TIMPs) are specific inhibitors of MMPs that also possess growth-promoting properties. 

Aims
 
To analyse the expression profile of MMP-2, MMP-9 and TIMP-2 in non-small cell lung cancer (NSCLC) and to assess the impact of expression on survival. 

Methods
 
This is a retrospective study of patients who underwent resection for stage I-IIIa NSCLC with a post-operative survival >60 days. Patient follow up was a minimum of 2 years. Standard ABC immunohistochemistry was performed on 4μm paraffin-embedded sections from the tumour periphery using monoclonal antibodies to MMP-2, MMP-9 and TIMP-2.

Results
 
The results of the immunohistochemistry are set out below. marker tumour expression log-rank survival stromal expression log-rank survival MMP-2 9/72 (13%) p=0.10 34/72 (47%) p=0.34 MMP-9 79/152 (52%) p=0.04* 69/152 (45%) p=0.84 TIMP-2 28/90 (31%) p=0.04* 66/90 (73%) p=0.90 Two or more 16/59 (27%) p=0.007* There were no associations between expression and clinicopathological findings for any tumour marker. There was co-expression of MMP-2 and MMP-9 in tumour cells (p=0.01). 

Conclusions
 
MMP-2, MMP-9 and TIMP-2 are expressed in NSCLC. MMP-9 and TIMP-2 tumour expression correlate with a poor outcome (both p=0.04) and are potential prognostic markers for NSCLC. Cumulative expression of two or more MMPs/TIMPs may also have increased prognostic significance. Proteases and their inhibitors are novel targets for therapeutic intervention and should be evaluated in NSCLC.
Abstract 21106: The Matrikine Proline-Glycine-Proline is Locally Generated Following Acute Arterial Vascular Injury
Authors: Gregory A Payne, Dongqi Xing, Liliana Viera, Jindong Li, Xin Xu, Patricia Jackson, J. Edwin Blalock, Amit Gaggar
Journal: Circulation (2017)

Introduction: Neointimal formation following vascular injury remains a clinically significant obstacle. Endovascular procedures, including percutaneous coronary intervention, disrupt the endothelium leading to inflammation and cellular proliferation within the vessel wall. Extracellular matrix (ECM) degradation by matrix metalloproteases (MMPs) has increasingly been understood to generate bioactive chemokines (i.e. matrikines) capable of causing cellular activation. Despite this knowledge, the contribution of matrikine signaling to vascular injury remains poorly understood. Hypothesis: We examined the hypothesis that the pro-inflammatory matrikines Proline-Glycine-Proline (PGP) and acetylated-PGP (AcPGP) are generated following acute arterial vascular injury. Methods: 20 male, c57bl/6 mice underwent unilateral carotid ligation of the left common carotid artery. Suture was passed, but not tied, under the contralateral carotid artery to serve as a sham procedure. Mice were sacrificed at Days 0, 1, 3 and 14 (n = 5 mice per day). Carotids and serum were harvested and processed for biochemical analysis. PGP and AcPGP were measured using liquid chromatography-tandem mass spectrometry, while total and pro-MMP9 was measured by ELISA. Results: Sham arteries had no significant induction of total or pro-MMP9 at any time. In contrast, ligated arteries showed a robust induction of both total and pro-MMP9 by Day 1 that was sustained through Day 14 (P &lt; 0.0001 compared to mean sham arteries at all days). Importantly, PGP concentrations from ligated arteries showed a significant and sustained increase compared to Sham arteries by Day 3 (mean 150 vs 20 pg/mg carotid, P &lt; 0.0001), while no difference was observed in AcPGP concentrations. Serum PGP and AcPGP concentrations remained low and unchanged throughout the 14-day experiment (mean ~100 and 20 pg/mL respectively). Conclusions: The current results identify PGP as a novel matrikine associated with acute vascular injury. AcPGP has previously been shown to activate endothelial cells to increase permeability and endothelin-1 synthesis via CXC Chemokine Receptor 2 (CXCR2). These results implicate PGP, a similar CXCR2 ligand, as a potentially novel mediator of inflammation following vascular injury.
NARROW BAND IMAGING IMPROVES PREOPERATIVE FLUORESCENCE ASSESSMENT OF UPPER AND LOWER AIRWAYS IN HEAD AND NECK CANCER PATIENTS
Authors: Phan Nguyen, Farzad Bashirzadeh, Julie Agnew, Robert Hodge, Ian Brent Masters, Camile Farah, Edwina Duhig, Belinda Clarke, David Fielding
Journal: Journal of Thoracic Oncology (2011)
Association of Preterm Birth With Risk of Ischemic Heart Disease in Adulthood
Authors: Casey Crump, Elizabeth A. Howell, Annemarie Stroustrup, Mary Ann McLaughlin, Jan Sundquist, Kristina Sundquist
Journal: JAMA Pediatrics (2019)

Preterm birth has previously been associated with increased risks of hypertension and diabetes, but not ischemic heart disease (IHD), in adulthood. The reasons for this lack of association with IHD despite associations with its risk factors have been elusive, but may be associated with methodologic issues, such as survivor bias, in prior studies.To determine whether preterm birth is associated with an increased risk of IHD in adulthood in a large population-based cohort.This national, population-based cohort study included all 2 141 709 persons who were born as singleton live births in Sweden during 1973 to 1994. The data were analyzed in September 2018.Gestational age at birth, identified from nationwide birth records in the Swedish Birth Registry.Ischemic heart disease that was identified from nationwide inpatient and outpatient diagnoses through 2015 (maximum age, 43 years). A Cox regression was used to examine gestational age at birth in association with IHD in adulthood while adjusting for other perinatal and maternal factors. Cosibling analyses assessed for potential confounding by unmeasured shared familial factors.Of 2 141 709 participants, 1 041 906 (48.6%) were female and there were 1921 persons (0.09%) who received a diagnosis of IHD in 30.9 million person-years of follow-up. Gestational age at birth was inversely associated with IHD risk in adulthood. At ages 30 to 43 years, adjusted hazard ratios for IHD associated with preterm (gestational age <37 weeks) and early-term birth (37-38 weeks) were 1.53 (95% CI, 1.20-1.94) and 1.19 (1.01-1.40), respectively, compared with full-term birth (39-41 weeks). Preterm-born women had lower IHD incidence than preterm-born men (15.16 vs 22.00 per 100 000 person-years) but had a higher adjusted hazard ratio (1.93; 95% CI, 1.28-2.90 vs 1.37; 95% CI, 1.01-1.84). These associations did not appear to be explained by shared genetic or environmental factors in families.In this large national cohort, preterm and early-term birth were associated with an increased IHD risk in adulthood. Persons born prematurely need early evaluation and preventive actions to reduce the risk of IHD.
Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise
Authors: Jeremy M. Robbins, Matthew Herzig, Jordan Morningstar, Mark A. Sarzynski, Daniel E. Cruz, Thomas J. Wang, Yan Gao, James G. Wilson, Claude Bouchard, Tuomo Rankinen, Robert E. Gerszten
Journal: JAMA Cardiology (2019)

Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions.To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training.This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018.Plasma DMGV levels.The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training.Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training.Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.
Let’s talk about the notion of cure
Authors: Amy D Robertson
Journal: BMJ (2019)

Let's talk about the notion of cureAmy Robertson describes how language around cure has shaped her understanding of wellness and the importance of seeing bodies with chronic conditions as resilient Amy D Robertson I first encountered the notion of cure as a little girl.I received a diagnosis of arthritis at the age of 2 and remission was a central part of conversations about my condition.Although I cannot recite the specifics, I distinctly remember the energy of those conversations.There was so much hopefulness that hinged on my going into remission, so much relief when it seemed that I had, and such deep sadness when my arthritis "came back."I took all of it in: the hope and the despair, the powerful notion that remission was the key to my wellness, and ultimately the sense that I was fundamentally broken and unwell.
Incidental Detection of Adenocarcinoma in the Neck of the Pancreas by FDG PET Imaging When a Cystic Lesion in the Body of Pancreas Was Evaluated
Authors: Haiqun Xing, Ya Hu, Bo Hou, Li Huo, Yupei Zhao
Journal: Clinical Nuclear Medicine (2019)

Abstract FDG PET/CT and PET/MRI were performed to evaluate a cystic lesion in the body of the pancreas in a 65-year-old man. Neither studies showed abnormally increased activity in the cystic lesion in the body of the pancreas. However, both studies revealed abnormal activity in the neck of the pancreas, which did not show anatomical abnormality and was not suspected prior to the PET imaging. Pathological examination demonstrated that the lesion in the body of the pancreas was a benign duct dilation, whereas the abnormal FDG activity in the neck of the pancreas was due to pancreatic adenocarcinoma.
Tumor‐Specific Transcripts Are Frequently Expressed in Hepatocellular Carcinoma With Clinical Implication and Potential Function
Authors: Qiupeng Zheng, Jingjing Zhao, Hui Yu, Huajie Zong, Xigan He, Yiming Zhao, Yan Li, Yu Wang, Yichao Bao, Yuchen Li, Bing Chen, Weijie Guo, Yilin Wang, Zhiao Chen, Yingjun Zhao, Lu Wang, Xianghuo He, Shenglin Huang
Journal: Hepatology (2019)

Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor‐specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues. Many of the TSTs were found to be unannotated and noncoding RNAs. We observed that intergenic TSTs are generated from transcription initiation sites frequently harboring long terminal repeat (LTR) elements. The strong presence of TSTs indicates significantly poor prognoses in HCC. Functional screening revealed a noncoding TST (termed TST1), which acted as a regulator of HCC cell proliferation and tumorigenesis. TST1 is generated from an LTR12C promoter regulated by DNA methylation and retinoic‐acid–related drugs. Additionally, we observed that TSTs may be detected in the blood extracellular vesicles of patients with HCC. Conclusion: Our findings suggest an abundance of TSTs in HCC and their potential in clinical settings. The identification and characterization of TSTs may help toward the development of strategies for cancer diagnosis and treatment.
Cerebellar Hypermetabolism in a Case of Paraneoplastic Cerebellar Syndrome With the Primary Lymphoepithelial Carcinoma in Tonsil
Authors: Jingnan Wang, Wenze Wang, Yang Zhao, Ruixue Cui
Journal: Clinical Nuclear Medicine (2019)

Abstract A 70-year-old man with cerebellar syndromes was clinically diagnosed as paraneoplastic cerebellar degeneration and underwent whole-body 18 F-FDG PET/CT imaging for screening primary tumor. Intensely elevated tracer uptake in both cerebellar hemispheres was revealed, whereas no abnormality was found in MRI. Increased tracer uptake and swelling of the left tonsil and a cervical lymph node were found at the same time, suggesting neoplasm in tonsil with lymph node metastasis. Pathological examination demonstrated lymphoepithelial carcinoma of the left tonsil.