tbuckley/cabot-search huggingface dataset:
Abstract B54: Molecular basis of oncogene cooperation in liver cancer
Authors: Asha Balakrishnan, Lionel Lim, Stefano Cairo, Sanjay Chandriani, Kirk D. Jones, Marie-Annick Buendia, Andrei Goga
Journal: Clinical Cancer Research (2010)

Abstract Combinations of genetic alterations in cancer genes lead to aberrant signaling properties and drive cellular transformation. Whether each oncogene gives rise to unique signals or combinations of oncogenes lead to new properties of cancer cells remains unclear. Using cell-based and animal model systems it has been shown that certain oncogenes can cooperate with each other to induce a fully malignant tumor phenotype. In addition, the combination of oncogenes and the extent of cooperation between them to give rise to a tumor may vary in different cancers. Cooperativity between MYC and RAS oncogenes has been observed in different cancer types. MYC is often overexpressed and sometimes amplified in cancer, while, activating RAS mutations occur in about 30% human cancers. Hepatocellular carcinoma (HCC) is among the four leading causes of cancer-related death. Currently, except for early surgical intervention or liver transplantation, no effective cures exist. Overexpression of both MYC and activated HRAS together in primary human liver tumors has been associated with aggressive forms of liver cancer with an especially poor prognosis. However, a systematic approach to understanding MYC and RAS cooperation in liver cancer has not yet been undertaken. We have discovered that transgenic mice overexpressing MYC, RAS or both MYC and RAS in their liver, give rise to distinct liver tumors. MYC and RAS coexpression led to faster tumor development and decreased survival. To gain a comprehensive view of the molecular changes that contribute to MYC and RAS oncogene cooperation in de novo liver tumors, we combined the conditional transgenic models of liver cancer with global gene expression, signaling pathway analyses and functional studies. Comparisons were made to clinically annotated human tumors and key pathways validated in cell lines and animal models. We show that tumors driven by either oncogene or a combination of both are phenotypically and molecularly distinct from each other with differential regulation of multiple genes and pathways. Our work suggests that MYC and RAS cooperate through specific genes, such as CCNE1 and multiple signaling pathways including proliferation, apoptosis, angiogenesis and multiple metabolic pathways, to contribute to liver cancer development. We also show molecular alterations across signaling pathways are comparable between mouse and human liver cancers. Primary human liver tumors can be segregated into distinct subsets based on differentially regulated gene sets from cooperating MYC and RAS tumors. These results indicate that molecular changes underlying MYC and RAS cooperation may serve as ideal molecular markers and therapeutic targets for liver cancer. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B54.
P259 Incidental findings on CT pulmonary angiography: what should we be looking for?
Authors: R. Thiagarajah, M. Qureshi, A. Sahu, R. Riordan
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> The role of diagnostic imaging in pulmonary embolism (PE) is being increasingly undertaken by CT pulmonary angiography (CTPA) and there has been an explosion of usage in our trust in the last two years, which reflects a growing trend in clinical practice in the United Kingdom (UK). There has been an abundance of literature on how best to utilise CTPA with particular attention to optimisation of pulmonary artery opacification to aid diagnosis. An additional benefit of CTPA over other modalities for the diagnosis of PE that may be less widely appreciated is CTPAs ability to provide simultaneous information on other pathologies affecting the thorax and alternative diagnoses requiring further clinical management. <h3>Methods</h3> To this cause a sample of 400 CTPAs were retrospectively reviewed in a 1001 bed acute teaching hospital in the UK, to identify the common types of additional pathology demonstrated. The presence of PE and any additional pathology, with special attention to “incidental” pathology, or pathology that was unsuspected but which was significant enough to change the patient9s management was recorded, in order to identify the common incidental pathologies that we should be actively hunting for when reviewing a CTPA. <h3>Results</h3> PE was demonstrated in 94 studies (22.6%; 95% CI 18.7% to 26.9%). Additional pathology was seen in 373 studies (89.7%; 95% CI 86.3% to 92.4%), of which 58 (15.6%; 95% CI 12.0% to 19.6%) were reported as incidental. These included coronary calcification, degenerative spine, aortic disease, valve disease, liver cyst, retro-sternal goitre, anatomical variant, gallstone/gallbladder disease, scapula lesion, rib fracture/deformity. Forty-three cases (10.3%) went on to require further investigation or follow-up. One hundred and ten caes (26.4%) showed no PE but an alternative diagnosis i.e. effusion/consolidation. <h3>Conclusion</h3> The prevalence of PE in our sample was 22%. Secondary findings were found in 89.7% of scans, with completely incidental findings reported in 15.6% and an alternative diagnosis when there was no PE in 26.4%. This emphasises the usefulness of CTPA in supplying further diagnostic data in patients with suspected PE.
Unusual F-18 Choline Uptake in Penile Metastasis From Prostate Cancer
Authors: Marina Hodolič, Jure Fettich, Marino Cimitan, Borut Kragelj, Stanley J. Goldsmith
Journal: Clinical Nuclear Medicine (2012)

Functional imaging of prostate carcinoma is important especially for restaging of the disease in the case of biochemical relapse. The powerful imaging modality F-18 choline PET/CT (FCH PET/CT) improves assessment of clinically silent sites of recurrence. Despite rich vascularization and vascular communication between the penis and the prostate, metastatic involvement of the penis is relatively infrequent. We present a prostate cancer patient with unusual FCH uptake in a penile metastasis from prostate cancer. Metastasis from prostate adenocarcinoma to the bulbus and corpus of penis was identified with FCH during follow-up, 3 years after the initial diagnosis.
Female Veterans Seek Answers: Vietnam Cancer Risks in Question
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Female Veterans Seek Answers: Vietnam Cancer Risks in Question Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 19, 7 October 1992, Pages 1462–1463, https://doi.org/10.1093/jnci/84.19.1462 Published: 07 October 1992
Abstract P5-06-11: Knockdown of Splicing Factor SRp20 Results in Cell Line-Dependent Apoptosis in Breast Cancer Cells
Authors: T-T Ho, AD Arslan, WT Beck, X. He
Journal: Cancer Research (2010)

Abstract Background: Cancer-specific alternative splicing as well as aberrant splicing factor expression in tumors have been reported (Korner M et al, Am. J. Pathol. 175:461-472, 2009). Splicing factor SRp20 belongs to a family of highly conserved serine-arginine-rich proteins with multiple functions in RNA processing such as spliceosome assembly and alternative splicing (Graveley BR, RNA. 6(9):1197-211, 2000). Materials and Methods: We established stable MDA-MB-231, MCF-7, and T47D cell lines carrying doxycycline (Doxy)-inducible SRp20shRNA and assessed Doxy-induced knockdown (KD) of SRp20 by western blot. We performed cell growth curves in triplicate using the MTT assay to determine the effect of SRp20 KD in these cell lines after Doxy induction of SRp20shRNA, and compared these to controls. For apoptosis assays, we stained SRp20shRNA sublines with Hoechst 33342 and counted apoptotic cells under the microscope. We also carried out western blots to examine the expressions of Bcl-2 and cleaved caspases-3, -6, -7, and -9. Results and Discussion: We found that the expression of SRp20 was upregulated in immortalized human mammary epithelial cells (HMECs), compared to controls, and that the level of SRp20 correlated with the transformation state. Knockdown of SRp20 was seen to be 88%, 58%, and 52% in MDA-MB-231, MCF-7, and T47D cells, respectively. However, SRp20 KD suppressed breast cancer cell growth in a cell line-dependent manner. Cell growth after 7 days was decreased in estrogen receptor-negative (ER-) MDA-MB-231 cells (91.4%), and estrogen receptor-positive (ER+) MCF-7 (73.2%), while SRp20 KD had no effect on growth of ER+ T47D cells. The differences between MCF-7 and T47D were notable, since SRp20 was suppressed by -50% in both lines. We found that the number of apoptotic cells in MDA-MB-231 line remarkably increased after Doxy treatment, indicating that the inhibition of cell growth was due to apoptosis. Further, immunoblot analysis of Bcl-2 and cleaved caspases in MDA-MB-231 cells indicated that the SRp20 KD activates the intrinsic apoptotic pathway in these breast cancer cells. We are presently assessing the expressions of these proteins in MCF-7 and T47D cells and investigating the mechanistic basis for this cell line-dependent effect of SRp20 KD. In summary, we report here a novel finding that inhibition of splicing factor SRp20 inhibits cell growth in some breast cancer cell lines. The intrinsic apoptotic pathway appears to be the main mechanism of cell growth inhibition in these cells. Our results indicate that SRp20 plays a major role in the survival of some breast cancer cell lines. This splicing factor may represent a novel therapeutic target for the treatment of some breast cancers. (Supported in part by CA40570 and CA138762 from NCI to WTB, in part by IDPH to XH, and in part by UIC) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-11.
PTU-144 Small-bowel capsule endoscopy for iron deficiency anaemia alone; experience from a tertiary centre
Authors: D E Yung, J H Lam, S Douglas, A Koulaouzidis, J N Plevris
Journal: Gut (2012)

<h3>Introduction</h3> Small-Bowel Capsule Endoscopy (SBCE) is a useful diagnostic modality in the investigation of Obscure Gastrointestinal Bleeding (OGIB). Its role though in Iron Deficiency Anaemia (IDA) is less clear. <h3>Aim</h3> To assess the usefulness of SBCE in the diagnostic work-up of patients with IDA with neither complicating pathology nor specific GI symptomatology. <h3>Methods</h3> <i>Design:</i> Retrospective study. <i>Setting:</i> University hospital &amp; tertiary referral centre for capsule endoscopy for South East of Scotland. A review of SBCE database was carried out for the period between March 2005 and June 2011. Only patients with IDA and no other GI symptoms or known previous diagnosis contributing to IDA for example, Crohn9s or coeliac disease were included in the analysis. Electronic and paper case notes were reviewed for information relating to procedure indications, investigations carried out prior to SBCE and subsequent findings. Cases with failed examinations due to SBCE retention and/or incomplete small-bowel transit were excluded from further analysis. SBCE findings were classified as clinically significant (small-bowel malignancy, significant inflammation and/or strictures and coeliac disease) or clinically relevant pathology that is, angioectasias (P1/P2 lesions). <h3>Results</h3> A total of 811 SBCE examinations were performed during the above period. IDA as the sole indication for SBCE was recorded in 27% (<i>n</i>=221; 151F/70M, mean age: 62 yr) patients. All patients had bi-directional endoscopies prior to SBCE. The overall diagnostic yield (DY) of SBCE was 30.7% (68/221). The DY for significant pathology and angioectasias was 9% and 21.7%, respectively. In those ≤40 yr (<i>n</i>=20; 13F/7M, mean age: 26.5 yr), significant pathology was found in 25% (5/20); in the &gt;40 yr group (<i>n</i>=201; 138F/63M, mean age: 72.2 yr), significant pathology was found in 7.5% (15/201), p=0.0231. Although none of the patients ≤40 yr had angioectasias, P1 or P2 lesions were found in 48/201 (21.7%) of those &gt;40 yr, p=0.009. Age-range analysis showed angioectasias in 11.1%, 13%, 20% and 42% in the age-groups 41–50, 50–60, 60–70, 70–80 yr, respectively. Interestingly, in those &gt;80 yr (<i>n</i>=16; 12F/4M, mean age: 82.5 yr) angioectasias were present in 50% of SBCE but no significant pathology was identified. <h3>Conclusion</h3> IDA alone is one of the main indications (27%) for referral to the SBCE service of our centre with the majority of referrals coming from the &gt;40 age group. In our cohort, the overall DY of SBCE for IDA is 30.7% and the commonest finding small-bowel angioectasias. The detection rate of significant small-bowel pathology for those &gt;40 yr is low decreasing to zero in the &gt;80 age group. In contrast, 25% of patients ≤40 yr had a significant or sinister diagnosis made with SBCE. <h3>Competing interests</h3> None declared.
835 RBV BLOOD CONCENTRATION AT FIRST WEEK OF PEG-IFN/RBV/TVR COMBINATION THERAPY IS A GOOD PREDICTIVE MARKER OF RENAL DYSFUNCTION AND ANEMIA
Authors: Y. Karino, I. Ozeki, S. Hige, M. Miyakawa, M. Kimura, T. Arakawa, T. Nakajima, Y. Kuwata, T. Sato, T. Ohmura, J. Toyota
Journal: Journal of Hepatology (2013)
AB0519 Relationship between Various Psychological Problems with the Disease Activity or Damage Indices in Patients with Sle
Authors: J.S. Song, S.T. Choi, E.H. Park, J.I. Kang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic inflammatory disease in which almost every organ may be affected. Various psychological problems are associated with systemic conditions, but the influence of SLE is still a matter of discussion. <h3>Objectives</h3> We evaluated depression, anxiety, anger, fatigue and quality of life in patients with SLE, compared to healthy controls. We also investigated the relationship between these psychological problems, disease activity and damage in patients with SLE. <h3>Methods</h3> 108 patients with SLE and 52 healthy controls completed a psychological questionnaire. Psychological parameters were assessed as follows: depression, Center for Epidemiologic Studies Depression Scale (CES-D); anxiety, Hospital Anxiety and Depression Scale (HADS); anger, State Trait Anger Expression Inventory (STAXI); fatigue, the Profile of Mood States fatigue-inertia scale (POM); quality of life (QOL), Functional Assessment Chronic Illness Therapy (FACIT). Disease activity and damage indices were measured by the SLE Disease Activity Index (SLEDAI) and the SLE Collaborating Clinics/American College of Rheumatology (SLICC/ACR), respectively. <h3>Results</h3> Patients with SLE showed higher symptoms of depression, anxiety, anger and fatigue (<i>p</i>=0.005; <i>p</i>=0.057; <i>p</i>=0.044; <i>p</i>=0.020, respectively), and lower level of QOL (<i>p</i>=0.003) than healthy controls. In the patients with SLE, mood symptoms such as depression, anxiety, and anger were correlated with each other (depression and anxiety: <i>r</i>=0.710, <i>p</i>&lt;0.001; depression and anger: <i>r</i>=0.602, <i>p</i>&lt;0.001; anxiety and anger: <i>r</i>=0.546, <i>p</i>&lt;0.001). Fatigue and QOL were closely correlated with mood symptoms, respectively. The patients with higher prednisolone use (&gt;7.5 mg/day) showed higher levels of depression, anxiety, anger and fatigue (<i>p</i>=0.002; <i>p</i>=0.022; <i>p</i>=0.027; <i>p</i>=0.010, respectively), and lower level of QOL (<i>p</i>=0.001) than the patients with lower prednisolone use (≤7.5mg/day). However, there were no significant differences in evaluating these parameters according to disease activity or damage indices. <h3>Conclusions</h3> The patients with SLE had higher levels of depression, anger and fatigue and lower level of QOL compared to healthy controls. Psychological parameters were affected by daily glucocorticoid dose rather than disease activity or damage indices. These findings suggested that the comprehensive evaluation of the various psychological problems could be helpful to SLE patients, especially those with higher doses of glucocorticoid, even if disease activity and damage are not severe. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4112
Esophageal perforation due to removal of partially covered self-expanding metal stents placed for a benign perforation or leak
Authors: M. Hirdes, F. Vleggaar, K. Van der Linde, M. Willems, E. Totté, P. Siersema
Journal: Endoscopy (2010)

Benign esophageal perforations and anastomotic leaks can be effectively managed by stent placement. However, when partially covered self-expanding metal stents (SEMS) are used, safe removal may be complicated. In this case series, we evaluated the complicated removal of SEMS placed for a benign esophageal perforation or leak in four patients. In all patients a partially covered SEMS was placed. After a median stent time of 29 days (range 21 - 30), the SEMS were found to have become embedded in the esophageal wall. Endoscopic removal resulted in perforation in all patients. All patients recovered uneventfully, although one patient underwent esophagectomy. If uncovered SEMS ends become embedded, removal of the stent may cause major damage to the esophageal wall. It is therefore recommended to remove embedded partially covered SEMS only after first placing a fully covered SEMS or self-expanding plastic stent inside this stent to necrotize the ingrown tissue at the uncovered stent ends.
CS-21 * EphA2 PROMOTES INFILTRATIVE INVASION OF GLIOMA STEM CELLS IN VIVO THROUGH CROSSTALK WITH Akt AND REGULATES STEM PROPERTIES
Authors: H. Miao, N. Gale, H. Guo, J. Qian, A. Petty, J. Kaspar, A. Murphy, D. Valenzuela, G. Yancopoulos, D. Hambardzumyan, J. Lathia, J. Rich, J. Lee, B. Wang
Journal: Neuro-Oncology (2014)

Diffuse infiltrative invasion is a major cause for the dismal prognosis of glioblastoma (GBM), but the underlying mechanisms remain incompletely understood. Using human glioblastoma stem cells (GSCs) that recapitulate the invasive propensity of primary GBM, we find that EphA2 critically regulates GBM invasion in vivo. EphA2 was expressed in all seven GSC lines examined, and overexpression of EphA2 enhanced intracranial invasion. The effects required Akt-mediated phosphorylation of EphA2 on serine 897. In vitro the Akt-EphA2 signaling axis is maintained in the absence of ephrin-A ligands and is disrupted upon ligand stimulation. To test whether ephrin-As in tumor microenvironment can regulate GSC invasion, the newly established Efna1;Efna3;Efna4 triple knockout mice (TKO) were used in an ex vivo brain slice invasion assay. We observed significantly increased GSC invasion through the brain slices of TKO mice relative to wild type littermates. Mechanistically EphA2 knockdown suppressed stem properties of GSCs, causing diminished self-renewal, reduced stem marker expression and decreased tumorigenicity. In a subset of GSCs, the reduced stem properties were associated with lower Sox2 expression. Overexpression of EphA2 promoted stem properties in a kinase-independent manner and increased Sox2 expression. In addition to suppressing invasion, disrupting Akt-EphA2 crosstalk attenuated stem marker expression and neurosphere formation while having minimal effects on tumorigenesis, suggesting that the Akt-EphA2 signaling axis contributes to the stem properties. Taken together, the results show that EphA2 endows invasiveness of GSCs in vivo in cooperation with Akt and contributes to the maintenance of stem properties.
Chilaiditi's Syndrome on Tc-99m Hexamethylpropylene Amineoxime Imaging
Authors: QAISAR H. SIRAJ, BRIAN S. McGLONE
Journal: Clinical Nuclear Medicine (1999)

A 71-year-old man with ulcerative colitis, which was clinically unresponsive to steroid therapy, was evaluated because of an acute exacerbation of his disease. A Tc-99m-labeled hexamethylpropylene amineoxime leukocyte scan was performed to assess the site, extent, and severity of the disease. This information was necessary in considering the suitability of surgical resection and to aid surgical planning. The scan showed prominent increased uptake in the right side of the colon, which was seen to be interposed between the liver and the diaphragm-Chilaiditi's syndrome. The presence of active inflammatory bowel disease in the interposed segment of the colon subsequently was confirmed at colectomy.
Abstract 3633: Prognostic value of chromogranin A and alkaline phosphatase in patients with advanced neuroendocrine tumor
Authors: Monica Ter-Minassian, Jennifer A. Chan, Susanne M. Hooshmand, Lauren K. Brais, Anastassia Daskalova, Rachel Heafield, Zhiron Qian, Xihong Lin, David C. Christiani, Matthew H. Kulke
Journal: Cancer Research (2012)

Abstract BACKGROUND: Serum chromogranin A (CgA) or alkaline phosphatase (ALP) are often assessed in patients with advanced neuroendocrine tumor (NET) patients but their prognostic significance continues to be debated. We evaluated whether elevated CgA or ALP levels were associated with shorter survival in a large, prospectively collected cohort of NET patients. METHODS: We identified patients with metastatic NET enrolled in an institutional database between 2003-10. We used the single measurement of serum CgA or ALP levels collected with shortest time after metastatic diagnosis and classified them as binary variables (elevated/normal) based on clinical laboratory specification of elevated value. Elevated biomarker levels were correlated with overall survival using the log-rank test. Hazard ratios for each biomarker were calculated using multivariate Cox regression, adjusting for baseline characteristics of age, gender, tumor histology, and tumor subtype. Each biomarker was modeled as a time-varying covariate to account for variability in time from initial metastatic diagnosis to time of biomarker test. RESULTS: We identified 526 patients who presented at our institution with metastatic NET. Of these, 349 had available CgA values and 350 had available ALP values. There were 146 and 153 deaths among those tested for CgA and ALP, respectively. The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated CgA was 5.98 (5.04, 7.3), as compared to 13.27 (9.51, -) for those at normal CgA limits (p&amp;lt;0.0001). The median survival time from time of metastatic diagnosis (yrs, (95%CI)) for patients with elevated ALP was 4.51 (3.27, 5.93), as compared to 8.87 (7.07, 9.64) for those at normal ALP levels (p=0.0001). Using the adjusted time-varying model, either elevated CgA (aHR 3.97 (2.73, 5.75) p=3.15E-13) or elevated ALP (aHR 2.4 (1.7, 3.4) p=7.96E-07) were adverse prognostic factors for patients with advanced NET. Elevated CgA was significantly associated with shorter survival in all NET subgroups (pancreatic NET, carcinoid, other NET). Elevated ALP was also a predictor of shorter survival in advanced NET patients, with the exception of those with advanced pancreatic NET. CONCLUSION: Elevated serum CgA or elevated ALP is an independent adverse prognostic factor in patients with advanced NET. 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 3633. doi:1538-7445.AM2012-3633
P635Proarrhythmic drugs exert hERG-independent slowing of relaxation and irregular beating in rat engineered heart tissue
Authors: A Eder, A Hansen, C Neuber, S Schaaf, MA Vos, T Eschenhagen
Journal: Cardiovascular Research (2014)

Background: The assessment of proarrhythmic risks of drugs remains challenging. We evaluated the suitability of rat engineered heart tissue (EHT).