tbuckley/cabot-search huggingface dataset:
Abstract 3621: The multi-tyrosine kinase inhibitor Sunitinib reduces prostate cancer growth through autocrine and paracrine mechanisms
Authors: PAUL A. NGUEWA, Roque Díaz Díaz, Miriam Redrado, María Collantes, Ivan Peñuelas, Irene Manrique Saenz, Diego Serrano, Alice Agliano, Alfonso Calvo
Journal: Cancer Research (2010)

Abstract Prostate cancer (PrCa) is the most common malignancy and the second leading cause of cancer death in men. Although localized PrCa can be successfully cured, advanced hormone refractory tumors are resistant to current therapeutic regimes. Therefore, novel approaches for effective malignancy control are still required. Molecular targeted therapies have emerged as promising alternatives to classical chemo/radiotherapy. The clinical benefit of the multi-tyrosine kinase inhibitor Sunitinib, which blocks the activity of receptors such as PDGFR, VEGFR1/2, FLT3, and c-KIT has been proven in renal carcinoma, GIST, and neuroblastoma. In this work, we have tested the therapeutical efficacy of sunitinib against PrCa both in vitro and in vivo, using the androgen-independent cell line PC-3. These cells express target receptors PDGFRa/b, and VEGFR1/2. Sunitinib dramatically reduced cell proliferation in vitro (P&amp;lt;0.0001) in a dose-dependent manner (with an IC50 of 1-2 micro-M) and colony formation (P&amp;lt;0.0001), through an autocrine mechanism. Moreover, when combined with doses of 2 and 4 Gy ionizing radiation, sunitinib enhanced the inhibitory activity of radiotherapy in colony formation assays. In vivo experiments revealed that PC3 tumor-bearing mice treated with 80 mg/Kg/day sunitinib had significantly smaller tumors (63% reduction) than controls. A single dose of 6 Gy caused tumor shrinkage by 80%, whereas the combination of both therapies resulted in more than 90% tumor reduction, suggesting that sunitinib could be used as a radiosensitizer. Positron emission tomography (PET) analyses with 18-FDG, FMISO, and FLT tracers showed a decrease in glucose uptake, hypoxia, and cell proliferation, respectively, in sunitinib-treated mice, as compared to controls. Immunohistochemical analysis for CD-31 revealed an expected reduction in tumor angiogenesis in sunitinib-treated tumors in comparison with untreated tumors. Overall, these data support the use of sunitinib as a clinically relevant drug for the treatment of PrCa. 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 3621.
Abstract 1394: Acute bacterial infection increases lung cancer metastasis via toll-like receptors 2 and 4
Authors: Simon C. Chow, Carlos HF Chan, Mathieu C. Rousseau, Jonathan Cools-Lartigue, Lucie Roussel, Betty Giannias, Heewon Yoon, Crystal Chen, Lorenzo E. Ferri
Journal: Cancer Research (2012)

Abstract INTRODUCTION: Surgery is required for curative treatment of lung cancer but is associated with a high rate of bacterial infections such as pneumonia. There is emerging clinical evidence to suggest that infectious complications may decrease survival after cancer surgery, but the mechanism is unclear. Interactions between bacteria and host cells are mediated by specialized pathogen recognition receptors, of which the Toll-like receptors (TLRs) are best characterized. We and others have shown that cancer cells express TLRs, but their function is largely unknown. The aim of this study is to investigate the mechanisms of bacterial infection-facilitated lung cancer metastasis with a particular focus on the role of TLRs. METHODS: Two lung cancer cell lines (murine H-59 and human A549) were incubated a) directly with heat-inactivated bacteria (S.pneumonia or E.coli) or purified bacterial antigens (lipopolysaccharide or lipoteichoic acid), or b) indirectly with an in vitro pneumonia model using conditioned media from pulmonary bronchial epithelial cells incubated with heat-inactivated bacteria or bacterial antigens. Migratory and metastatic ability of thus treated cells were determined in vitro (adhesion, migration) and in vivo (hepatic intravital microscopy and intra-splenic liver metastasis). A clinically relevant in vivo model of severe infection, cecal ligation and puncture (CLP) or sham control, was employed in some animals. To assess the role of TLRs, we used transgenic TLR4 knockout mice, and small molecule inhibiting molecules or antibodies of TLRs. RESULTS: Direct and indirect (in vitro pneumonia) infection of H-59 and A549 increased adhesion to extracellular matrix components approximately 2-8 fold and 2-4 fold over negative control, respectively. In vitro pneumonia increased in vitro migration of H-59 approximately 2-5 fold. Direct and indirect incubation of H-59 with S.pneumonia and E.coli increased the in vivo adhesion to liver sinusoids 2-4 fold. CLP (in vivo infection model) enhanced the in vivo adhesion of H-59 3-fold and increased number of liver metastases at 2 weeks post-injection approximately 12 fold. These effects were attenuated in TLR4 -/- mice and with TLR2 and TLR4 inhibition. CONCLUSION: Activation of TLR2 or TLR4 on lung cancer cells, either directly by S.pneumonia and E.coli, indirectly though activated bronchial epithelial cells, or via an in vivo infection, increases cancer cell adhesion, migration and metastasis. TLRs thus represent a potential therapeutic target in bacterial infection facilitated cancer metastasis. 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 1394. doi:1538-7445.AM2012-1394
Case 18-2007
Authors: Donald S. Kaufman, W. Scott McDougal, Anthony L. Zietman, Robert H. Young
Journal: New England Journal of Medicine (2007)

A 54-year-old man came to the Multidisciplinary Genitourinary Clinic of the Cancer Center for advice on management of prostate cancer. A slowly rising serum prostate-specific antigen level led to a needle biopsy of the prostate 2 weeks after the consultation. Examination of the biopsy specimens revealed adenocarcinoma, with a Gleason score of 7, involving the left lobe. A treatment recommendation was made.
Diffuse Liver Uptake on 99mTc-MDP Bone Scan Secondary to Severe Hepatic Failure
Authors: Paul Chen, Theodore Marentis, Richard K.J. Brown
Journal: Clinical Nuclear Medicine (2014)

Hepatic uptake on an MDP bone scan is a non-specific finding. When present, the etiology needs to be determined. The differential diagnosis depends on the pattern of uptake. Metastatic breast and colon cancer are frequent causes of focal faint uptake. Diffuse uptake is rare, but can be seen with hepatitis, amyloid, and IV gadolinium administration. In addition, aluminum breakthrough from the molybdenum generator can cause colloid formation and subsequent diffuse hepatic uptake. We present a case of diffuse uptake in a patient with acute hepatic failure. The etiology of the failure was extensive thrombosis of the inferior vena cava (IVC).
Psoas Abscess Revealed by Gallium SPECT/CT
Authors: Wei-Ning Du, Chin Hu, Daw-Guey Tsay, Nan-Jing Peng
Journal: Clinical Nuclear Medicine (2011)

Psoas abscess is an uncommon condition that can be easily misdiagnosed if planar scintigraphy alone is used. Single photon emission computed tomography (SPECT)/CT is superior to planar imaging because it can usually eliminate the problem of misdiagnosis. We describe a case of a 70-year-old woman with intermittent pyrexia and gradual onset of left hip pain for 2 days. Planar scintigraphy with technetium-99m methylene diphosphonate and gallium-67 citrate revealed radiotracer accumulation on the left side of the vertebral column at the L4–L5 level and the left sacroiliac joint. SPECT/CT scan revealed gallium-67 accumulation not only in the aforementioned osteomyelitic regions but also in the left psoas muscle, which was finally identified as a psoas abscess. The spatial and anatomic information provided by SPECT/CT, which helped identify the occult infection, was more accurate than that by conventional planar imaging modalities.
SAT0043 Impaired B cell immunity in IL-27R knock-out mice in collagen induced arthritis
Authors: O.B.J. Corneth, A.-M.C. Mus, P.S. Asmawidjaja, L. Kil, R.W. Hendriks, E. Lubberts
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Collagen induced arthritis (CIA), a mouse model for rheumatoid arthritis, is both B cell and T helper (Th) 17 cell mediated. Interleukin 27 receptor (IL27R) signaling upregulates IL12 receptor expression on naïve T cells and inhibits Th17 differentiation. In addition, IL27R expression is upregulated on activated B cells. However, the role of IL27R signaling on B cells is not fully understood. We therefore aim to investigate the role of IL27R signaling in B cell immunity and the pathogenesis of CIA. <h3>Objectives</h3> To investigate the role of IL27R signalling on B cells in CIA. <h3>Methods</h3> For CIA, mice were immunized with complete Freund’s adjuvant and chicken collagen type II (CFA/CII) and boosted 21 days later. For AIA, mice were immunized with CFA and methylated bovine serum albumin (mBSA) and 7 days later a stimulus with mBSA was given directly in the knee joint. For B cell activation experiments, mice were immunized with DNP-Ficoll and sacrificed 7 days later. <h3>Results</h3> IL27R knockout mice showed a decreased CIA arthritis score compared to wild type controls. Analysis of B cells in CIA by immunohistochemistry and flow cytometry showed severely decreased germinal center formation in IL27R knockout mice. In addition, plasma cell formation and auto-antibody formation were decreased compared to controls, suggesting an intrinsic defect in B cell differentiation upon activation. To exclude that the phenotype of IL27R knockout mice in CIA was caused by a defect in Th17 pathogenicity, we made use of the Th17 mediated antigen induced arthritis (AIA) model, which is B cell independent. IL27R knockout animals developed comparable arthritis to controls. Based on these data we concluded that T cells respond normally in these mice. We therefore further analyzed B cell responses using the T cell independent DNP-Ficoll immunization model. IL27R knockout mice showed lower IgM and IgG3 plasma cell counts in spleen and lower DNP specific IgM and IgG3 antibody levels in serum. These data further support impaired B cell differentiation after activation. <h3>Conclusions</h3> Here we show that IL27R knockout mice are protected against full blown CIA. Th17 cells in these mice are functionally normal. However, terminal B cell differentiation appears to be impaired, suggesting a critical role for IL27R signaling in B cell immunity. <h3>Disclosure of Interest</h3> None Declared
Abstract LB-394: Type II topoisomerases contribute to nitric oxide-induced DNA breakage during cancer-related inflammation
Authors: Tsai-Kun Li, Yu-Chen Yang, Tang-Long Shen
Journal: Cancer Research (2012)

Abstract Activated inflammatory leukocytes generate a variety of reactive nitrogen and species (RNOS) which have been proposed to contribute to genome instability and cancer development. We previously reported that oxidative stress induces topoisomerase II (TOP2)-mediated DNA breaks via TOP2 cleavable complex (TOP2cc) formation. Moreover, drug-induced TOP2αcc and TOP2βcc are suggested to be anti-cancer and carcinogenic, respectively. Here we show that either inflammation-produced or chemical-released nitric oxide (NO), like TOP2-targeting etoposide (VP-16), induce TOP2cc-meidated DNA breakage, mutagenesis and carcinogenesis: (i) NO-releaser S-nitrosoglutathione (GSNO) induces formation of skin melanomas in 9,10-dimethyl-1,2-benzanthracene (DMBA)-initiated mice; (ii) the co-culture experiments revealed that inflamed macrophages causes activation of DNA damage response and chromosome DNA breakage in target cells (iii) NO production and two TOP2 isozymes are responsible for the generation of chromosome DNA breaks; (iv) consistently, treatment of a NO releaser GSNO induces hTOP2αcc and hTOP2βcc formation; (v) GSNO also increases mutation rate and kill cells in TOP2-dependent manner; and (vi) the incidences of GSNO- and VP-16-induced melanomas are found to be lower in skin-specific top2β-knockout mice. Thus, our results provide the first demonstration for the functional role of TOP2 in the NO-caused DNA damage, mutagenesis and carcinogenesis. The TOP2 involvement in pathological settings such as chronic inflammation-associated mutagenesis and subsequent cancer development were discussed. 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 LB-394. doi:1538-7445.AM2012-LB-394
Abstract B9: Germline conservation of hypermutable codons in gatekeeper tumor suppressor genes implicates pro-carcinogenic CpG sites <i>in vivo</i> as anti-teratogenic ‘shock absorbers’ <i>in utero</i>
Authors: Yongzhong Zhao, Richard J. Epstein
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Methylated CpG sites are readily mutated, yet are strongly conserved in tumor suppressor genes. Uniquely, the arginine-encoding CGA codon may undergo methylation-dependent point mutation to a stop codon (TGA), whereas the arginine-encoding AGA codon is stable. To clarify the relationship between germline codon mutability and somatic carcinogenesis, we compared patterns of codon usage in tumor suppressor gene subsets known to differ in function and evolutionary stability. Procedures: Human tumor suppressor genes were classified as either pro-apoptotic (gatekeepers; high-essentiality, low Ka/Ks) or repair-type (caretakers; low-essentiality, high Ka/Ks). Reference normal and tumor gene sequence databases were analysed in terms of nucleotide composition (GC%), intragenic CpG sites, and CGA/AGA codon patterns. Phylogenetic analyses of relevant codon frequencies across 24 species from the UCSC database were performed as a control. Results: Species-specific stop codon frequency varies with genomic GC content in a methylation-regulated manner, whereas CGA frequency is GC-independent. Whole-genome frequencies of CGA and TGA codons are positively correlated (p = 0.013). CGA mutation in tumors is asymmetric (TGA &amp;gt;&amp;gt; CAA; p &amp;lt; 0.001), with such mutations 3-fold more likely to be nonsense-type in gatekeepers than in caretakers. Non-random CGA clustering is demonstrable in canonical gatekeepers such as NF1, Rb and TP53 (p &amp;lt; 0.02). Conclusion: Human pro-apoptotic suppressor genes are selectively enriched for the presence of nonsense-prone CpG-containing codons involved in somatic adult-onset tumor progression. We propose that this germline vulnerability is conserved as part of a methylation-dependent embryonic response to environmental teratogens which otherwise cause excessive apoptosis, somatic malformations, and reduced fitness. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B9
Abstract 1980: Transcriptional profiling in peripheral blood mononuclear cells of patients with pancreatic cancer identifies several genes with potential diagnostic and prognostic implications
Authors: Micahel Baine, Subhankar Chakraborty, Lynette Smith, Kavita Mallya, Aaron Sasson, Surinder Batra
Journal: Cancer Research (2010)

Abstract Background: Pancreatic cancer is one of the most lethal human malignancies, being the fourth most common cause of cancer-related mortality in the Western world and fifth most common worldwide. Despite advancements in understanding the pathogenesis of this malignancy, no reliable screening test currently exists for pancreatic cancer. As a result, the majority of patients present with advanced stage disease contributing to a poor prognosis. Owing to their accessibility, peripheral blood mononuclear cells (PBMCs) are a rich source of potential biomarkers for diagnosis and predicting patient outcome. The question of whether the gene expression profile in PBMCs of pancreatic cancer patients could be useful for its detection has not been examined. Hence, we tested the hypothesis that global gene expression profiling of PBMCs from pancreatic cancer patients could be useful to identify genes potentially useful as specific, early, surrogate biomarkers in the diagnosis of lethal pancreatic cancer. Experimental design: We evaluated the transcriptional profile in PBMCs of 35 patients with pancreatic adenocarcinoma and compared it to that of 33 healthy controls using a Phalanx whole genome microarray containing probes for 39,200 genes. The Universal human reference was used as the reference against which all samples were normalized. We further validated the results of the microarray by quantitative real time PCR using SYBR green based chemistry. The normalization of the data was performed using the BRB Array tool software (http://linus.nci.nih.gov/BRB-ArrayTools.html) Results: After normalization and filtering the genes (criteria: false discovery rate &amp;lt;10%, confidence level 90%), 21,671 genes remained for analysis. 530 genes were found to be differentially expressed in pancreatic cancer patients (p&amp;lt;0.05). 78 of these genes had at least a 1.5 fold change (up or down-regulation) in expression compared to that in the control PBMCs. The expression of two significantly upregulated genes (GAPDH, ASGR2) and four significantly down-regulated genes (DYRK2, MS4A1, EDG1, GRAMD1C) were validated via quantitative PCR. There was an 83% correlation between the microarray and qPCR results for these genes. Conclusion: The present study represents the first example of gene expression profiling in the PBMCs of pancreatic cancer patients with the aim of identifying patterns of gene expression for diagnostic and prognostic purposes. 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 1980.
OPTIMIZING ELECTROCARDIOGRAM INTERPRETATION AND CATHETERIZATION LABORATORY ACTIVATION IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: A TEACHING MODULE FOR MEDICAL STUDENTS
Authors: Mortada Shams, Alexander Sullivan, Shajidan Abudureyimu, Bassel Hassouna, Vimala Jayanthi, Richard Amdur, P. Jacob Varghese, Marco Mercader
Journal: Journal of the American College of Cardiology (2016)
Methodology and personality in Briquet's syndrome: a reappraisal
Authors: M J Kaminsky, P R Slavney
Journal: American Journal of Psychiatry (1976)

The authors describe a case of Briquet's syndrome in a man and discuss the relationship of that condition to personality features. They view Briquet's syndrome as a set of behaviors arising from personality traits and suggest that examination of the genesis and treatment of the condition be shifted to a characterological approach.
Abstract 3199: Ceramide restores the expression of wild-type p53 tumor suppressor in mRNA splicing through PP1 and ASF/SF2.
Authors: Yong-Yu Liu, Gauri A. Patwardhan
Journal: Cancer Research (2013)

Abstract p53 mutants that have been detected in approximately 50% of tumors loss the activity in stabilizing the genome and tumor suppression, and further exhibit oncogenic function in cancer cells. Most tumors that exhibit disrupted p53 signaling pathways remain addicted to p53 mutants, and p53 mutants have emerged as perhaps the most important target to improve cancer treatment. Most works in restoring p53 activity focus on either altering protein conformations of the mutants or introducing foreign p53 gene into cells. Using gene silencing strategy and mass spectrometry, here we demonstrated that ceramide modulates the RNA splicing to restore the expression of wild-type p53 in p53 deletion-mutant ovarian cancer cells. Enhanced endogenous long-carbon chain ceramide species (C16- to C24-ceramides) and exogenous C6-ceramide, but not other sphingolipids, restored wild-type p53 mRNA (intact exon-5), phosphorylated p53 protein (Ser15 in exon-5) and p53-responsive proteins (p21, Bax) in cells that dominantly expressed a deleted p53-mRNA and protein in exon-5. Thus, the restored p53 sensitized the cells to induced apoptosis. Furthermore, ceramide activated protein phosphatase 1 (PP1), rather than PP2a, increased the translocation of alternative splicing factor ASF/SF2 from cytoplasm to nucleus and thus determined the pre-mRNA splicing for wild-type p53. Alternative pre-mRNA splicing not only generates more than one protein isoform from single gene, it also results in gene mutants in cancer and other diseases. Our study elucidates a previous unrecognized mechanism in regulating the expression of wild-type versus mutant protein of p53 and indicates mutants can be restored in posttranscriptional levels by using an epigenetic approach. Citation Format: Yong-Yu Liu, Gauri A. Patwardhan. Ceramide restores the expression of wild-type p53 tumor suppressor in mRNA splicing through PP1 and ASF/SF2. [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 3199. doi:10.1158/1538-7445.AM2013-3199
Risk of Kidney Failure Associated with the Use of Acetaminophen, Aspirin, and Nonsteroidal Antiinflammatory Drugs
Authors: Thomas V. Perneger, Paul K. Whelton, Michael J. Klag
Journal: New England Journal of Medicine (1994)

People who take analgesic drugs frequently may be at increased risk of end-stage renal disease (ESRD), but the extent of this risk remains unclear.
PWE-071 The management of small early rectal cancers—network MDT results: Abstract PWE-071 Table 1
Authors: A R G Sheel, L Titu, P Skaife, P S Rooney, S Myint
Journal: Gut (2012)

<h3>Introduction</h3> A regional Small and Early Rectal Cancer (SERC) MDT was established in 2008 with input from Gastroenterology, TEMS service, pathologists, oncologists, cancer specialist nurses and surgeons. All patients with stage 1 rectal cancer are referred, ensuring cases suitable for local excision (LE) are managed by teams with appropriate expertise in line with NICE guidance and peer review measures for colorectal cancer.<sup>1 2</sup> We aimed to review the outcome of patients managed by the MDT focusing on adequacy of treatment according to histology, follow-up and classical surgery. <h3>Methods</h3> Observational study of the SERC MDT database. <h3>Results</h3> The SERC MDT processed 137 referrals (62 f: 75 m. Median age 77 (range 36–90)). There were 48 malignant cases. Of 74 local excision (LE) procedures, 24 were performed for malignancy (see Abstract PWE-071 table 1 below for outcomes). Classical surgery was advised for nine patients. The stoma averse or surgically high-risk patients were offered direct radiotherapy (n=16). There were 14 attempted LE9s prior to MDT referral. All were malignant and only three were completely excised. Incompletely excised lesions were referred for classical surgery or radiotherapy. <h3>Conclusion</h3> This regional SERC MDT has demonstrated the successful implementation and functioning of the early rectal cancer MDT model. All small rectal lesions should be referred to MDT prior to attempt at LE, thus allowing for accurate staging and appropriate pre-operative planning. R0 resection rates need improvement. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <i>Guidance on Cancer Services—Improving Outcomes in Colorectal Cancer: Manual Update</i>. NICE, 2001. 2. <i>Case Study: Implementing Early Rectal Cancer MDTs in Secondary Care</i>. November 2011.