tbuckley/cabot-search huggingface dataset:
Abstract 1273: Metabolic networks and the role of LDHB in breast cancer
Authors: Jennifer B. Dennison, Jennifer R. Molina, Huifang Guo, Gordon B. Mills
Journal: Cancer Research (2011)

Abstract Gene expression data of breast cancer cell lines and patient tumors reveal several distinct subtypes that demonstrate different metabolic phenotypes. Our goal was to determine what metabolism genes contribute to the metabolic phenotypes. We hypothesized that dichotomous expression of metabolism genes would identify key drivers of cell metabolism. To select candidate genes, we completed a bimodal analysis using microarray data from 59 breast cancer cell lines. To generate a metabolic network, dichotomous genes were selected from known or probable metabolic networks including electron transport, TCA cycle, nutrient transport, pentose phosphate shunt, energy requiring pathways, and glycolysis. Two groups of dichotomously expressed genes emerged from this analysis: TCA cycle anaplerotic genes (including PFKP, GLS) and cataplerotic/biosynthetic genes (including FASN, GLUL, and FBP1). The gene with the highest bimodal index was LDHB that encodes lactate dehydrogenase B. For breast cancer cell lines, LDHB mRNA and protein were most highly expressed in ER-, glycolytic cell lines. LDHB is reported by others to be part of a “MYC signature,” and consistent with this hypothesis, for ER- cell lines, LDHB mRNA levels were highly associated with MYC and glutaminase, a metabolic down-stream target of MYC. For patient tumors, LDHB mRNA expression was also bimodal with the highest expression in basal-like cancers. Elevated expression of LDHB mRNA predicted worse clinical outcomes for patients with Her2 positive and triple negative tumors. Compared to normal-like breast tissue from patients, LDHB mRNA expression was elevated in triple negative tumors. We conclude that LDHB may be a target of MYC and contribute to the glycolytic phenotype of triple-negative tumors. 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 1273. doi:10.1158/1538-7445.AM2011-1273
Abstract 5445: Suberoylanilide hydroxamic acid induces Epstein-Barr virus lytic cycle and enhanced apoptosis in nasopharyngeal carcinoma
Authors: Kwai Fung Hui, George Sai-Wah Tsao, Alan Kowk-Shing Chiang
Journal: Cancer Research (2010)

Abstract Nasopharyngeal carcinoma (NPC) has uniquely high prevalence in Southern Chinese populations and a predilection to affect young adult males. Epstein-Barr virus (EBV) is harbored in every tumour cell of NPC but it persists in tightly latent form expressing few viral proteins and evading the immune system. Induction of EBV lytic cycle will lead to expression of a much larger number of viral proteins which may serve as potential therapeutic targets against the cancer. We reported that suberoylanilide hydroxamic acid (SAHA), a FDA-approved histone deacetylase inhibitor, could strongly induce viral lytic cycle in EBV-positive gastric carcinoma cells. Here, we demonstrated that SAHA (at 5-10 μM) could potently induce EBV lytic cycle in a panel of EBV-positive NPC cell lines, as evidenced by increased viral DNA replication, expression of immediate early (Zta and Rta), early (BMRF1) and late (VCA-p40 and gp350/220) viral lytic proteins and production of infectious viral particles. Immunofluorescent staining demonstrated expression of viral lytic proteins in more than 40% of the NPC cells. Enhanced killing of EBV-positive NPC cells when compared with that of EBV-negative counterparts was observed and cleaved form of PARP was predominantly expressed in EBV-positive than EBV-negative NPC cells, following treatment with SAHA for 24, 48 and 72 hours. The kinetics of expression of cleaved PARP correlated with that of Zta viral protein in EBV-positive NPC cells. In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent and mediates enhanced apoptosis of NPC cells. Further investigation into SAHA's development as a novel virus-targeted therapeutic drug in NPC is warranted. This work is funded by EBV research and NPC AoE grants of AKSC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5445.
Management of deep looping when failing to progress at double-balloon enteroscopy
Authors: E. Despott, A. Murino, C. Fraser
Journal: Endoscopy (2011)

Deep intubation of the small bowel during double-balloon enteroscopy (DBE), as described by Yamamoto et al. [1] [2] [3], relies on the principles of minimal small-bowel stretching and loop reduction. This is achieved by simultaneous traction provided by the enteroscope and overtube balloons, combined with a “pull-back” maneuver that allows loop resolution and straightening of the free and untethered small bowel [1]. In our experience and that of others [4], this insertion method may be unsuccessful, for example when small-bowel tethering due to intra-abdominal adhesions occurs in patients, because deep loops are formed that are difficult to reduce when the enteroscope is advanced. The result is a decreased insertion depth and a higher rate of failure for the procedure. We describe an adaptation of the conventional insertion method that may be useful when deep looping occurs during DBE.
Efficacité au long cours et risques liés à la mucosectomie des polypes duodénaux extra-ampullaires
Authors: JM Canard, E Samaha
Journal: Endoscopy (2012)

L'efficacité au long cours de la mucosectomie duodénale des polypes extra ampullaires et les risques liés à cette procédure sont peu connus, car les séries sont petites et les complications importantes.
Abstract 3264: Downregulation of intersectin-1s in human lung cancer may contribute to tumorigenesis
Authors: Dan Predescu, Jin Zhang, Monal Patel, Cristina Bardita, Sanda Predescu
Journal: Cancer Research (2012)

Abstract The expression of intersectin-1s (ITSN-1s), a granzyme B (GrB) substrate and one of the trisomic genes that may provide protection against most cancers in Down's syndrome, is significantly downregulated in human lung cancer (LC) cells and tissue. To date, there is no information on the cellular and molecular factors that modulate ITSN-1s expression or whether downregulation of ITSN-1s can contribute to LC. Thus, we hypothesize that loss of full-length ITSN-1s due to proteolytic cleavage by GrB during an inflammatory response and the interplay between the signaling events triggered by the two cleavage products, are part of a complex common molecular mechanism involved in the oncogenic transformation of cells. To address this hypothesis, we used cultured LC cells and tissue, as well as a range of biochemical (Western blot, ELISA, BrdU incorporation), molecular biology (plasmid DNA transfection, qPCR), morphological (immuno-histochemistry, fluorescence microscopy) approaches, soft agar colony formation and xenograft tumor formation in nude mice to evaluate whether downregulation of ITSN-1s can contribute to lung carcinogenesis. Western blot and immuno-histochemistry of LC cells and lung tissue lysates showed significant decrease in ITSN-1s protein levels, while qPCR revealed only slight decrease, if any, in ITSN-1s mRNA. In vitro studies showed that GrB cleaves ITSN-1s and generates a cleavage fragment (GrB-EHITSN) with high proliferative potential. Lung epithelial cells expressing the GrB-EHITSN show 40% increase in BrdU incorporation, selective activation of p38MAPK and downstream Elk-1 transcription factor. These findings are consistent with a p38MAPK and Elk-1 pro-proliferative signaling pathway regulated by ITSN-1s. Activation of p38 and Elk-1 was also detected by western blot using phospho-specific antibodies, in all LC cells investigated. Expression of the two GrB cleavage fragments of ITSN-1s, individually or together, in human lung epithelial cells exerts a modulatory effect on the balance p38/Erk1/2MAPK activation. Functional studies showed that ectopic expression of ITSN-1s in the LC cells restored the p38/Erk1/2MAPK balance, significantly reduced their proliferation rate as well as the formation of colonies in soft agar and xenograft tumors in nude mice. Altogether, our results suggest that downregulation of ITSN-1s can promote the oncogenic transformation of cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3264. doi:1538-7445.AM2012-3264
Abstract 4511: LY2801653 treatment increases survival of mice bearing H441 orthotopic lung tumors
Authors: Wenjuan Wu, Chen Bi, Mark T. Uhlik, Julie A. Pomeroy, Hong Gao, Kelly M. Credille, Richard A. Walgren, Chuan Shih, Jonathan M. Yingling, Wei Yang
Journal: Cancer Research (2010)

Abstract Lung cancer is the leading cause of cancer-related death for both men and women in the world. c-Met receptor tyrosine kinase (RTK) signaling pathway has been implicated in tumor growth, angiogenesis, and metastasis. Sustained activation, over-expression, or mutation of c-Met is associated with poor prognosis in several tumors, including NSCLC. Therefore, c-Met is emerging as a novel target of therapeutic potential for lung cancer. We have discovered and developed a novel, ATP competitive, and orally active small molecule inhibitor of c-Met, LY 2801653. It is a potent inhibitor of c-Met phosphorylation in vivo, and demonstrated anti-tumor activity in several xenograft tumor models. In the current study, we evaluated the efficacy of LY2801653 in both c-Met dependant and c-Met independent NSCLC cells in vitro and in vivo orthotopic lung models that recapitulated the local and regional growth pattern seen in lung cancer patients. In c-Met dependant H441 model, LY2801653 demonstrated the significant inhibition of both primary tumor (90% inhibition) and metastasis (65% inhibition of lymph node and 70% inhibition of chest wall); whereas in c-Met independent H1299 model, LY281653 only inhibited primary tumor growth (70% inhibition). The benefit of LY2801653 treatment was further demonstrated in the survival of mice bearing H441 lung tumors. Treatment with LY2801653 significantly increased the survival of mice to 192% compared to that in the vehicle treated mice. The anti-tumor and/or anti-metastasis mechanism of LY2801653 was also investigated. These results demonstrated therapeutic potential of LY2801653 in the treatment of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4511.
Lymphedema of the Upper Limb
Authors: Mayo Weiss, Rüdiger G. H. Baumeister, Andreas Frick, Jens Wallmichrath, Peter Bartenstein, Axel Rominger
Journal: Clinical Nuclear Medicine (2014)

The aim of this study was to evaluate by lymphoscintigraphy the functional outcome after autologous lymph vessel transplantation (Tx) of the upper limb.One hundred seventy-seven patients (172 female, 5 male; median age, 56 years; range, 12-84 years) presenting with Tx situs in an upper limb were included. For correlation of scintigraphic data versus reduction of volume (RV) surplus measurements, we examined at 4 different time points as follows: preoperatively (T0), within 2 weeks after Tx (T1), 6 to 12 months after Tx (T2), and 32 to 38 months after Tx (T3). An additional long-term follow-up after at least 8 years (T4) was available in some cases.The maximum individual postoperative observation period was 19 years. In 169 of 177 cases, lymphedema had been caused by treatment of breast cancer (mastectomy, n = 103/169; breast preserving, n = 66/169) and/or radiation therapy (n = 130/177), but 2 patients presented with primary lymphedema. The remaining 6 cases of lymphatic disorders were caused by treatment of malignant melanoma, Hodgkin lymphoma, axillary Ewing sarcoma, non-Hodgkin lymphoma, hemangioma, or abscess removal.At T1, the mean RV of the affected limb was 73%, and the mean improvement of transport index (TI) was 28%. At T2, the RV was 64% and the TI was 23%, and at T3, the RV was 63% and the TI was 25%. Long-term follow-up after at least 8 years (T4: range, 9-19.2; mean, 14.1 years) was available in 19 of 177 patients, in whom persistent improvement in the scintigraphic data (25% decrease in TI) was confirmed by a mean clinical RV of 68%. The mean overall correlation was by a factor of 2.64.Our findings in this large set of patients undergoing autologous lymph vessel Tx to an upper limb confirm that this microsurgical technique significantly and persistently improves lymph drainage in patients with lymphedema. The findings of lymphoscintigraphy correlated well with volume measurements at long-term follow-up.
270 CD44+/EPCAM− PHENOTYPE IN HEPATOCELLULAR CARCINOMA (HCC) CELLS CORRELATES WITH INCREASED AUTOCRINE TGF-BETA AND MESENCHYMAL TRAITS
Authors: J. Fernando, A. Alvarez-Barrientos, E.B. Cepeda, E. Bertran, P. Sancho, I. Fabregat
Journal: Journal of Hepatology (2012)
Abstract 1103: An abnormally stiff microenvironment supports the overabundance of fibroblasts in non-small cell lung cancer.
Authors: Marta Puig, Alícia Giménez, Roland Galgoczy, Roberto Lugo, Josep Ramírez, Abel Gómez-Caro, Pere Gascón, Noemí Reguart, Jordi Alcaraz
Journal: Cancer Research (2013)

Abstract Breathing demands our lungs to be soft and elastic. In contrast, lung tumors exhibit an abnormal tissue hardening concomitantly with an altered lung architecture and function, which brings the mechanical microenvironment of the tumor closer to that of muscle or bone. This tissue hardening has been associated with the abundant reactive stroma rich in activated fibroblasts (also referred to as tumor associated fibroblasts or TAFs) that is a hallmark of non-small cell lung cancer (NSCLC). However, it remains unknown whether tissue hardening alone is sufficient to drive the abnormal abundance of fibroblasts in the stroma of NSCLC. To address this question, we cultured the human lung fibroblast cell line CCD-19Lu or primary human lung fibroblasts on collagen-coated polyacrylamide gels exhibiting normal- or tumor-like stiffness in the absence (0%) or presence (0.1%) of serum for 5 days. Primary cells were isolated from both tumor-free regions (referred to as control fibroblasts) or tumors of NSCLC patients diagnosed with either Adenocarcinoma (ADC, n=5) or Squamous Cell Carcinoma (SCC, n=5) histological subtypes. We observed a significantly higher density of CCD-19Lu fibroblasts in tumor-like gels compared to normal-like gels regardless the presence of serum. Similar results were obtained in both primary control fibroblasts and SCC-TAFs. In contrast, tumor-like gels induced a weaker density increase in ADC-TAFs. The increased fibroblast density in the tumor-like gels was associated with increased survival rather than proliferation, as revealed by a downregulation of caspase-3 and a rise in AKT phosphorylation. Our results indicate that extracellular hardening alone is sufficient to induce an increased density in lung fibroblasts by activating pro-survival pathways and suggest an abnormal response of ADC-TAFs to extracellular mechanical cues. Collectively these findings underline a major role of tissue hardening in the abnormal abundance of TAFs in NSCLC, particularly in the SCC subtype. These data may be useful in developing novel targeted therapies against the pro-survival effects of tissue hardening in SCC-TAFs, which act as co-conspirators of tumor progression. Citation Format: Marta Puig, Alícia Giménez, Roland Galgoczy, Roberto Lugo, Josep Ramírez, Abel Gómez-Caro, Pere Gascón, Noemí Reguart, Jordi Alcaraz. An abnormally stiff microenvironment supports the overabundance of fibroblasts in non-small cell lung cancer. [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 1103. doi:10.1158/1538-7445.AM2013-1103
PROPOFOL EN BOLOS VS. INFUSIÓN CONTINUA PARA LA SEDACIÓN DIRIGIDA POR ENDOSCOPISTAS DURANTE LA COLONOSCOPIA AMBULATORIA: UN ESTUDIO ALEATORIZADO
Authors: J Molina Infante, JM González Santiago, M Fernández Bermejo, E Martin Noguerol, C Martínez Alcalá, G Vinagre Rodríguez, M Hernández Alonso, C Dueñas Sadornil, B Pérez Gallardo, JM Mateos Rodríguez
Journal: Endoscopy (2011)

Introducción: El uso del propofol en infusión continua (IC) podría evitar que un miembro de la enfermería se dedicara únicamente a la monitorización del paciente y a la administración del propofol.
Pancreatic cysts with borderline CEA: Report from a single center
Authors: P Pinto-Marques, SJ Rulyak, MD Saunders, JH Hwang, MB Kimmey
Journal: Endoscopy (2006)

Background & aims: Pancreatic mucinous neoplasms exhibit variable malignant potential. Cyst fluid carcinoembryonic antigen (CEA) levels have good accuracy to differentiate mucinous from nonmucinous cysts. We sought to evaluate our population with borderline cyst fluid CEA. Materials and Methods: Retrospective single center study. Patients who underwent EUS–FNA of a pancreatic cyst, with fluid CEA between 5–800 ng/mL were selected and classified as intermediate (5–199 ng/mL) or high (200–800 ng/mL). Mann-Whitney test and Spearman correlation were applied as appropriate. Results: Sixty-one patients with a mean age of 61.2±13.0 were selected. Results of cytology included: Mucinous (2); Non mucinous (22); Malignancy (3); non diagnostic (17). Median cyst fluid CEA was 67.0 (IQR 22.9–132.3). There was no correlation between cyst size and CEA. Thirteen patients had surgery (table 1). In those, CEA was higher in mucinous cystadenoma compared with IPMT (median 213.3 vs. 47.0; p 0.03). Follow-up was limited to 9 cases (n=5 with intermediate CEA; n=4 with high CEA), for a median of 187.0 days (IQR: 77.0–381.5). CT scans were available in 7/9 and revealed no enlargement of the cyst. There was 1 complication (puncture of the common bile duct). Discussion: FNA-cytology results were generally poor. If both cytology and pathology were available (n=9), the former provided the diagnosis in only 2 cases (pseudocyst; ductal adenocarcinoma). Among patients with intermediate CEA, surgery revealed 7 mucinous neoplasm (one IPMT had HGD) and 1 malignant cancer which reinforces the need for close surveillance if surgical resection is deferred. In general, IPMT tend to have a lower CEA compared with mucinous cystadenomas. Lastly, most lesions selected for follow-up were unchanged, but a larger study with longer follow-up is needed to confirm this finding. In summary, a cyst fluid CEA between 5–200 ng/ml does not exclude a mucinous neoplasm. Additional studies are needed to address the natural history and the role for serial imaging studies and CEA measurements.
AB0775 Predictors of osteopenia in a uk population referred for dexa scanning
Authors: K. Mitchell, M. Bukhari, P. Diggle
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is acknowledged that the majority of fragility fractures occur in osteopenic individuals<sup>1</sup>. It is not known whether the traditionally defined risk factors for osteoporosis are synonymous with those of osteopenia. Neither is it known whether osteopenia in the spine or the femoral neck are better predictors of future fracture risk. <h3>Objectives</h3> To identify and define the predictors of osteopenia in the femoral neck and lumbar spine in an observational cohort of patients referred for DEXA scanning in the North West United Kingdom. <h3>Methods</h3> Patients referred for a first DEXA scan at the Rheumatology outpatient department at the Royal Lancaster Infirmary between June 2004 and August 2012 were identified and their data were included in the analysis. Data collected included: age at scan, gender, ethnicity, indication information and densitometry measurements of the femoral neck, total femur and lumbar spine. Two groups of patients were identified at each anatomical site: the 'control' group with normal bone density (T score &gt;-1.0) and an osteopenic group (Tscore &lt; -1 and &gt;-2.5). A student's T test was performed to analyse differences in continuous variables and odds ratios were calculated to assess risk factors of a binary nature using a logistic model. <h3>Results</h3> For the femoral neck, data were available on a total of 9262 patients, of which 4241 were in the control group and 5021 in the osteopenic group. At the lumbar spine, data were available on a total of 9310 patients, of which 5573 were controls and 3737 osteopenic. Densitometry data from both sites were available from 8437 patients, therefore the majority of patients feature in both site analyses. Tables 1 and 2 show differences between continuous variables of the two groups at the two sites analysed. Odds ratios for risk of osteopenia with the presence of a classical risk factor for osteoporosis are listed in table 2. <h3>Conclusions</h3> Osteopenic individuals are significantly older, shorter and lighter. Low BMI and previous fracture predict osteopenia but other traditional risk factors for osteoporosis are unreliable predictors of osteopenia in this cohort. Differences exist between predictors of osteopenia at the two sites. Further research is needed. <h3>References</h3> Arch Intern Med. 2004 May; 164(10):1108-1112. <h3>Disclosure of Interest</h3> None Declared