tbuckley/cabot-search huggingface dataset:
Abstract 5421: Sensitivity to dichloroacetate is determined by PDK expression.
Authors: Bevan P. Gang, Melissa Rooke, Sheenu Mishra, Jane E. Dahlstrom, Anneke C. Blackburn
Journal: Cancer Research (2013)

Abstract The Warburg effect occurs in 90% of tumours, where there is a high rate of glycolysis even in the presence of oxygen. This results in increased lactate production and reduced pyruvate oxidation. Dichloroacetate (DCA) is used clinically for congenital lactic acidosis and can reverse the Warburg effect by inhibiting the pyruvate dehydrogenase kinases (PDKs), activating pyruvate dehydrogenase thus promoting oxidative metabolism of pyruvate. The PDKs have different sensitivities towards DCA inhibition (PDK2&amp;gt;PDK4&amp;gt;PDK1&amp;gt;&amp;gt;PDK3). We have investigated the effects of DCA on cancer growth in vivo and in vitro, and examined the expression of the PDK isoforms to explain variation of cancer cell responses to DCA. DCA halted the growth of established V14 mouse mammary tumours in vivo, but was ineffective against 4T1 mouse mammary tumours. In 8 human cancer cell lines of breast, colon, pancreatic and prostate origin, 5 mM DCA (48 hr) inhibited growth by 5-40% in vitro. Western blotting for expression of PDK isoforms revealed that the most sensitive T-47D cells expressed PDK2 and low levels of the other PDKs, whereas less sensitive cells expressed high levels of PDK1 and/or PDK3. In siRNA knockdown (kd) experiments, PDK3-kd in MCF7 cells (low DCA sensitivity, high PDK3 levels) increased sensitivity to DCA by 30%, while DCA did not further inhibit growth of PDK2-kd T-47D cells, confirming that sensitivity to DCA growth inhibition is determined by the PDK profiles. PDK1 &amp; 3 are up-regulated in hypoxia, which may reduce the effectiveness of DCA. To the contrary, DCA increased apoptosis in hypoxia in MCF7 cells, suggesting that DCA can enhance effects of other stressors/drugs, an area of ongoing investigation. Use of the PDK profiles to target DCA sensitive tumours will improve the outcomes of clinical trials using DCA that are currently underway Citation Format: Bevan P. Gang, Melissa Rooke, Sheenu Mishra, Jane E. Dahlstrom, Anneke C. Blackburn, Cancer Metabolism and Genetics Group. Sensitivity to dichloroacetate is determined by PDK expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5421. doi:10.1158/1538-7445.AM2013-5421 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Place of colorectal stents in therapeutic management of malignant large bowel obstructions
Authors: S. Manfredi, C. Sabbagh, G. Vanbiervliet, T. Lecomte, R. Laugier, M. Karoui
Journal: Endoscopy (2014)

FFCD: T. Aparicio, Ph. Rougier, P. Michel, J.L. Legoux, O. Bouché, C. Lepage, R. Faroux, J. Taieb, E. Mitry.
Abstract 4645: Decreased CD4+ naive and effector memory T cell counts, and CD8+ naïve T cell counts, are associated with trichloroethylene exposure
Authors: H. Dean Hosgood, Luoping Zhang, Xiaojiang Tang, Roel Vermeulen, Min Shen, Martyn Smith, Chuangyi Qiu, Yichen Ge, Zhiying Ji, Jun Xiong, Boris Reiss, Zhenyue Hao, Songwang Liu, Yuxuan Xie, Weihong Guo, Noe Galvan, Laiyu Li, Nat Rothman, Hanlin Huang, Qing Lan
Journal: Cancer Research (2011)

Abstract Trichloroethylene (TCE) is a volatile chlorinated organic compound that is commonly used in the workplace as a degreaser for metal parts and general-purpose solvent for lipophilic compounds. Although TCE is considered an animal carcinogen, its carcinogenic potential in humans is uncertain. Occupational exposure to TCE has been associated with increased risk of kidney cancer and non-Hodgkin lymphoma in some studies, but findings are not fully consistent. We have carried out a cross-sectional study of 80 workers exposed to TCE and 96 unexposed controls matched on age and sex in Guangdong, China to study TCE's early biologic effects. We previously reported that the total lymphocyte count (but not the granulocyte count) and each of the major lymphocyte subsets (i.e., CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and B cells) were decreased in TCE-exposed workers compared to controls. These findings suggested a selective effect of TCE exposure on lymphoid progenitors and/or lymphocyte survival. To further study which subsets of lymphocytes are affected specifically, we investigated the effect of TCE exposure on the numbers of CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells by FACS analysis. Linear regression using the natural logarithm (ln) of each subset was used to test for differences between exposed workers and controls adjusting for potential confounders such as age, sex, smoking status, alcohol consumption, recent infections, and body mass index. We observed that CD4+ and CD8+ naïve T cell counts were about 8% (p = 0.056) and 17% (p = 0.0002) lower, respectively, among exposed workers. Strikingly, CD4+ effector memory T cell counts were decreased by about 20% among TCE exposed workers compared to controls (p = 0.001) whereas the CD4+ central memory T cell population was not significantly changed. Intriguingly, the numbers of CD4+ central memory T cells, and CD8+ memory T cells including central and effector memory population, as well as regulatory T cells were not significantly different between the controls and exposed workers. Thus, TCE selectively targets CD4+ naïve and CD4+ effector memory T cells, and CD8+ naïve T cells. These findings provide further insights into the biologic response of human immune cells upon exposure to TCE, which may include immunosuppression through reduced capacity to respond to antigens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4645. doi:10.1158/1538-7445.AM2011-4645
Abstract LB-304: Bone marrow-derived endothelial cells migrate to tumor sites and contribute to functional tumor vasculature
Authors: Aparecida M. Fontes, Ricardo Bonfim-Silva, Lucas Eduardo Botelho Souza, Fernanda Ursoli Ferreira Melo, Viviane Cassia Oliveira, Danielle Aparecida Rosa Magalhaes, Angelo A. Cardoso, Paula Rahal, Dimas Tadeu Covas
Journal: Cancer Research (2011)

Abstract Tumor expansion is dependent on neovascularization, a process that requires sustained new vessel formation. Although the critical role of angiogenesis by endothelial sprouting in this process, controversy still prevails on the whether vasculogenesis, involving bone marrow (BM)-derived endothelial cells, does contribute to this process. The objective of this study was to investigate the contributions of BM-derived endothelial cells to tumor vasculature, in a melanoma model using chimeric GFP mice. Methodology: First, wild-type C57BL/6 mice were was exposed to a single dose of 10 Gy X-irradition and rescued by transplantation of BM cells from C57BL/6-GFP mice. At d30 post-transplant, the animals received a subcutaneous infusion of melanoma cells stably transfected with the luciferase gene (B16/F10-Luc+). After 20 days, the tumors were harvested, and tumor stroma characterized using flow cytometry, bioluminescence-based image processing and confocal microscopy, to define the specific contribution of BM-derived cells. Results: Mice transplanted with donor GFP+ cells showed significant BM chimerism (90.9 ± 0.87%) demonstrating successful engraftment of donor BM stem/progenitor cells. Analyses of tumor specimens showed the presence of donor cells in the tumor sites (3.5±1.7%) in all animals, showing that BM-derived cells were effectively recruited to the developing melanoma. Interestingly, these cells represent endothelial cells (CD31+ cells; mean=X%) and myeloid-lineage cells (CD11b+ cells; mean=80%), but also tumor-infiltrating lymphocytes (CD8+ T cells, mean = 13.31; CD4+ T-cells, mean=2.1). Examination of the tumor endothelium by confocal microscopy clearly showed the presence of donor CD31/GFP cells in the vessel wall, namely in vessels lacking other mural components (as pericytes). Conclusions: Taken together, this study demonstrates that BM-derived cells are actively recruited to tumor sites, contributing to the tumor stroma and the formation of blood vessels in the developing tumor. We are performing studies to elucidate the molecular mechanisms involved in mobilization of of BM-derived precursor cells to the tumor microenvironment, and whether disruption of this vasculogeneic process significant impairs tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-304. doi:10.1158/1538-7445.AM2011-LB-304
Abstract P5-05-06: The Role of Sprouty 2 in HER2 Signaling in Breast Cancer; Decreased Expression Is Associated with Poor Outcome Including in Trastuzumab-Treated Patients
Authors: D Faratian, AH Sims, P Mullen, C Kay, I Um, SP Langdon, DJ. Harrison
Journal: Cancer Research (2010)

Abstract Purpose: Resistance to trastuzumab is a frequent clinical problem, in part due to the overriding activation state of the MAPK/PI3K signaling pathways. Sprouty-family proteins are negative regulators of MAPK/PI3K signaling, but their role in HER2 signaling and resistance to therapy is unknown. Experimental design: The association of Sprouty 2 gene expression with grade, HER2-status, and survival was investigated in a meta-analysis of 1107 breast tumors from six published microarray studies. Sprouty regulation in response to HER2/HER3 signaling was studied using qRT-PCR. Changes in expression of Spry2 and feedback inhibition on trastuzumab-resistance were studied using full-length/dominant-negative transfection or chemical inhibition in SKBr3 and BT474 cell lines in cell viability assays. Finally, expression of Spry2 was measured in a cohort of 122 patients treated with trastuzumab by quantitative fluorescence microscopy (AQUA). Results: Low Spry2 gene expression was associated with high HER2 protein expression. Spry2 was regulated through HER2/HER3 signaling as a delayed early gene, an effect reversed by treatment with the dimerization inhibitor pertuzumab. Overexpression of Spry2 in the SKBr3 trastuzumab-resistant cell line resulted in synergistic inhibition of cell viability with trastuzumab. Restitution of feedback inhibition with the PI3K-inhibitor LY294002 had a similar effect. Low Spry2 expression was associated with increased risk of death (HR = 2.28, 95% CI 1.22 - 4.26; p=0.008) in trastuzumab-treated patients, including in multivariate analysis (Cox regression analysis, p=0.002). Conclusions: These results suggest that combinations of negative regulators of growth factor signaling may be an effective therapeutic strategy in breast cancers with deficient feedback inhibition. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-06.
Abstract 4680: Exploring the relationships between genetic variants within the UGT1A locus, cellular detoxification and risk of bladder cancer
Authors: Wei Tang, Yi-Ping Fu, Luyang Liu, Natalia Orduz, Alpana Kaushiva, Adam Mumy, Patricia Porter-Gill, Timothy Meyers, Montserrat Garcia-Closas, Nuria Malats, Stephen Chanock, Francisco X. Real, Manolis Kogevinas, Nathaniel Rothman, Debra Silverman, Ludmila Prokunina-Olsson
Journal: Cancer Research (2011)

Abstract A recent genome-wide association study (GWAS) for urinary bladder cancer (UBC) has identified multiple novel genetic risk factors (Rothman et. al, Nat Gen, 2010). One of these factors was an intronic SNP rs11892031 (p=1.0×10-7) located within the UGT1A locus on chromosome 2q37. The human cellular detoxification uridine 5’ diphosphate (UDP)-glucuronosyltransferases (UGTs) belong to a superfamily of proteins that conjugate diverse endo and exotoxins, increase their solubility and facilitate their removal via bile and urine. The UGT1A locus includes nine protein-coding genes and four pseudogenes. Each first exon of these genes is regulated by its own promoter and is spliced to four constant exons producing nine UGT1A proteins. Due to the complexity of the region and ∼90-95% similarity between the substrate-binding exon 1 sequences of UGT1A genes, this region is poorly represented in public databases (HapMap, 1000 Genomes, dbSNP). To ensure specificity of detection, we generated long-range amplicons and sequenced all UGT1A exons in HapMap individuals (CEU) and in 44 bladder cancer patients and identified 25 non-synonymous coding variations. All these variations have been genotyped in 1000 bladder cancer cases and 1000 controls from the Spanish Bladder Cancer Study (SBCS). We found one exonic SNP that showed association stronger than the original GWAS variant, and multiple variants that showed some evidence of gene and cigarette smoking interactions. Having ∼20 coding and potentially functional variants within the UGT1A region, we are exploring methods of simultaneous analysis of individual variants and their haplotypes. In conclusion, association of genetic variants within the UGT1A region confirms that altered cellular detoxification of environmental substrates is an important factor for development of bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4680. doi:10.1158/1538-7445.AM2011-4680
Abstract P2-05-18: Deregulation of the Abl interactor 1 signaling as a potential biomarker for metastatic breast cancer.
Authors: Hongxing Tang, Paul Lockman, Yunxia Tao, Zonghan Dai
Journal: Cancer Research (2012)

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-18.
669 VALIDATION OF THE MESIAH SCORE AS PREDICTOR OF SURVIVAL IN HIV-INFECTED PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC)
Authors: N. Qazi, B. Mínguez, M. Ventura, M.B. Badshah, M.K. Jain, M. Harris, L.E. Taylor, L. Kikuchi, J. Marrero, N. Bräu
Journal: Journal of Hepatology (2013)
Upper gastrointestinal tumors
Authors: H. Künzli, B. Weusten
Journal: Endoscopy (2013)

Endoscopy Essentials Reviews in the Endoscopy Essentials series cite publications from the past year which, in the authors’ opinion, reflect the state-of-the-art in endoscopy. Alongside a short summary of each paper, authors explain why they consider their selected articles to be of importance.
Abstract 9351: Left Ventricular Torsion is Preload Dependent. A Study in Healty Volunteers After Blood Donation
Authors: Harun Kilic, Ugur Saygısunar, Mehmet Ayturk, Mustafa Gokhan Vural, Ramazan Akdemir
Journal: Circulation (2012)

Introduction: Left ventricular (LV) rotation plays an important role in LV contraction and relaxation. Hypothesis: Aim of this study is to investigate preload effect on LV torsion in normal volunteers of blood donation. Methods and Results: LV end-diastolic volume, LV apical and basal rotation, peak systolic LV Torsion were measured by speckle-tracking echocardiography in normal volunteers (n=26) before and after 450ml blood donation.Blood donation led to a significant decrease in end-diastolic LV internal diameter (48.7 + 0.4 versus 46.4+0.4 mm; P&lt;0.001) and cardiac output (6.2 + 1.0 versus 5.1+ 0.7 L/min; P&lt;0.001). There was a significant decrease in the magnitude of peak systolic apical rotation (4.4 +1.9° versus 2.9 + 1.5°; P&lt;0.001) but no change in basal rotation (2.6 +1.4° versus 2.7+ 1.6°; P=0.81). Peak systolic LV Torsion decreased after blood donation (6.9 +1.9 ° versus 5.7+2.1°; P=0.028). Conclusions: LV apical and peak systolic LV torsion are preload dependent. Preload changes should be considered when interpreting LV torsion
Chilaiditi Sign on 99mTc-Mebrofenin Hepatobiliary Scan Mimicking Bile Leak in Acute Cholecystitis
Authors: Suzanne Pascarella, Simin Dadparvar
Journal: Clinical Nuclear Medicine (2016)

Chilaiditi sign is the incidental radiologic finding of intestinal interposition between the liver and diaphragm, whereas Chilaiditi syndrome describes the presence of accompanying clinical symptoms including abdominal pain, constipation, vomiting, and respiratory distress. We describe a case of radiotracer accumulation over the liver dome on 99mTc-mebrofenin hepatobiliary scan performed on a 72-year-old man with acute cholecystitis mimicking a bile leak. However, chest radiograph and CT revealed intestinal hepatodiaphragmatic interposition. This case illustrates the importance of being familiar with the scintigraphic appearance of the Chilaiditi sign and correlating abnormal nuclear medicine scan findings with other available radiologic modalities.
Fistules après sleeve gastrectomie: apports de l'endoscopie interventionnelle
Authors: B Haddouche, I Iwanicki-Caron, E Ben Soussan, M Antonietti, R Alhameedi, A Di Fiore, JYO Touchais, P Michel, P Ducrotté, S Lecleire
Journal: Endoscopy (2013)

Les fistules après sleeve gastrectomie constituent une complication majeure potentiellement létale de la chirurgie bariatrique. La fermeture chirurgicale est associée à une morbi-mortalité importante. L'apport d'un traitement endoscopique reste à évaluer.
P1-08-09: Increased Mortality in Swedish Women Diagnosed with Breast Cancer during and Shortly after Pregnancy.
Authors: ALV Johansson, TM-L Andersson, S Cnattingius, C-C Hsieh, M Lambe
Journal: Cancer Research (2011)

Abstract Background: The incidence of pregnancy-associated breast cancer (PABC), i.e. breast cancer diagnosed during pregnancy or within two years after delivery, is increasing in Sweden. Results from epidemiological studies suggest that women with PABC have worse prognosis than women of same age and no recent birth. We studied the mortality in women with PABC, compared to women with a diagnosis of breast cancer not close to pregnancy, and in relation to when the PABC diagnosis occurred (during pregnancy, different postpartum periods). We also studied whether mortality varied over time since diagnosis. Materials and Methods: We used data from the Swedish National Cancer Register to identify all women diagnosed with breast cancer between ages 15–44 years during 1963–2002 (n=15,729). The study cohort was linked to the Multi-Generation Register to obtain information on childbirths and when they occurred. We estimated mortality rates among women with and without PABC, and subdivided by time of detection among PABC patients (PABC during pregnancy, or during months 1–3, 4–6, 7–12, 13–18, 19–24 after delivery). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using the novel method of flexible parametric survival models. These models use splines to model the baseline hazard rate, and are able to pick up more subtle time-dependent effects than the more commonly used piecewise splitting of the timescale (for example in Poisson regression). Results: Women with PABC had higher mortality than women diagnosed at the same age and calendar period and with no recent birth. In women with PABC (n=1,110), 46% died during follow-up, compared to 34% of the non-PABC patients (n=14,611). The mortality in both groups peaked at around two years after diagnosis, with the highest peak occurring in women diagnosed 4–6 months after delivery (HR=3.8, 95% CI 2.4−5.9). Also, among women diagnosed during pregnancy the mortality was higher compared to women diagnosed further away from delivery. An increased mortality among women with PABC remained up to 10 years after diagnosis. Discussion: Women with PABC had a poorer prognosis compared to women with breast cancer and no recent birth. The worse prognosis may be due to diagnostic delays or tumour promoting hormonal boosts or changes in the tumour micro-environment post-partum. Taken together, our findings indicate that women with PABC represent a high-risk group of young breast cancer patients that may require special management. Also, by applying novel statistical methods we were able to detect time dependent effects in that the elevated mortality associated with PABC varied by timing of diagnosis and time since diagnosis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-09.
Interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy
Authors: L. Allan, G Lamacraft, C M Price, A S J Prosser, P D Rogers, D Pounder, G D Schott, G. Titley, P D Collins
Journal: BMJ (1998)

Editor—Schott’s editorial questions the value of interrupting the sympathetic outflow in causalgia and reflex sympathetic dystrophy when clinical studies and meta-analyses fail to prove benefit.1 Continued use of terms such as “reflex sympathetic dystrophy” merely serve to perpetuate the misconception that sympathetic block should always be therapeutic. A consensus workshop in 1993 recommended a new taxonomy—accepted by the International Association for the Study of Pain—in which “complex regional pain syndrome” types I and II replace the terms reflex sympathetic dystrophy and causalgia respectively.2 Reclassification has significant advantages in the establishment of clinical criteria for diagnosis, which should lead to reduced use of numerous synonyms and different treatments. Clinically, the triad of autonomic, motor, and sensory symptoms and signs are variable, and laboratory investigations (thermography, skin blood flow, sudomotor function, and galvanic skin and ice response) are beyond the capability of many hospitals.3 The three phase bone scan is helpful in only 50% of cases.

Most authorities agree that the longer the pain remains untreated (with the concomitant disuse of the limbs), the greater the disability.4 Currently, referrals to pain clinics occur as a “last resort strategy,” so the result is a more difficult, complex treatment programme and a less successful outcome. The primary pain becomes complicated by secondary pain; gain phenomena; inability to perform daily, occupational, or recreational activities; inappropriate drug use; and even suicide.2 This is probably why single treatments, such as sympathetic blockade, do not provide complete pain relief in patients with long term symptoms.4 The clinical impression that smokers are refractory to sympathetic block therapy3 may also account for poor results. When diagnosis is definitive, with early referral for pain management we will be able to put therapeutic strategy to the ultimate test—a randomised controlled trial. Until then, editorials and papers presenting opposing views should be put in perspective, especially when the opposing views are presented by the same author.5
Genetic diversity and evolutionary relationships among Legionella pneumophila clinical isolates, Portugal, 1987 to 2012
Authors: M J Chasqueira, L Rodrigues, M Nascimento, M Ramos, T Marques
Journal: Eurosurveillance (2014)

The genetic diversity of 89 clinical Legionella isolates, collected between 1987 and 2012, in 22 hospitals from the five regions of Portugal, was analysed in this study using monoclonal antibodies (MAbs) of the Dresden panel and the sequence-based typing (SBT) protocol. The eBURST algorithm was used to infer levels of relatedness between isolates. All isolates collected were Legionella pneumophila, which were further characterised into four subgroups by MAbs, and 30 sequence types (STs) by SBT. Twelve of the STs were unique to Portugal; one of them (ST100) was represented by 32 epidemiologically related isolates. The ST44 was the profile with the highest number of epidemiologically unrelated isolates. The eBURST analyses indicate that, within the group formed by the 30 STs identified in this study, 17 STs were genetically close to at least another ST in the group. The comparison between the eBURST diagrams obtained with the STs from this study and the entire SBT database of the European Working Group for Legionella, showed that 24 (seven of them unique to Portugal) of our 30 STs were related with STs identified in others countries. These results suggest that the population of L. pneumophila clinical strains in Portugal includes both worldwide and local strains.