tbuckley/cabot-search huggingface dataset:
Abstract 4360: CD87 is essential for mediating growth-factor induced angiogenesis via distribution of integrin beta-1
Authors: Matthias Unseld, Marina Poettler, Rene Novotny, Christoph Zielinski, Gerald W. Prager
Journal: Cancer Research (2012)

Abstract CD87 (urokinase-type plasminogen activator receptor, uPAR) expression has been correlated with tumor progression most likely via its functional ole as a central receptor for extracellular proteolysis, but also via its role in initiating intracellular signal transduction. The role of CD87 in angiogenesis has recently been elucidated. Thus, we observed that in VEGF-stimulated ndothelial cells CD87 is essential for endothelial cell survival as well as for n efficient growth factor- induced endothelial cell migration. Thereby, the PI-anchored protein CD87 formed a complex with its ligand urokinase uPA) as well as the inhibitor plasminogen activator inhibitor-1 (PAI-1), which became redistributed to the leading edge via low density lipoprotein receptor- (LDLR-) like proteins. In this study, we analyzed the functional role of CD87 in integrin redistribution during growth factor-induced endothelial cell migration. CD87, thereby, directly interacted with integrin adhesion receptors (a5b1) as well as with LDLR- proteins. Either by interfering with CD87/integrin nteraction or by interfering with CD87/LDLR-protein interaction by using specific interfering peptides, we observed disruption of integrin redistribution to the leading edge in migrating cells. As a consequence diminished focal adhesion formations were observed and endothelial cell migration was diminished. In CD87-deficient HEK 293 cells as well as in endothelial cells derived from CD87 -/- mice, expression of CD87 mutants (mutL3/uPAR), which lacked the binding motif for LDLR, led to an impaired cell spreading as well as a diminished migratory response towards VEGF, while full length CD87 (wt/CD87) reconstituted this phenotype. That CD87 plays a central role in growth factor induced endothelial cell invasion and capillary-like tube formation in vivo was demonstrated by a directed in vivo angiogenesis assay (DIVAA), which was performed either in CD87 deficient or wild type animals in the presence or absence of interfering peptides. Our data give novel insights into the central role of CD87 in pro- angiogenic endothelial cell behavior as well as in its role in angiogenesis. Thus, CD87 might lead to a novel therapeutic strategies in tumor- angiogenesis. 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 4360. doi:1538-7445.AM2012-4360
Abstract LB-302: Inhibition of STAT3 following systemic delivery of STAT3 antisense oligonucleotide results in target inhibition in tumor and tumor-associated stromal cells and dramatic reduction in circulating pro-tumorigenic cytokines
Authors: Youngsoo Kim, Jeff Hsu, Tianyuan Zhou, Guobin He, Chris May, Brett P. Monia, Robert MacLeod
Journal: Cancer Research (2011)

Abstract Constitutive activation of STAT3 has been documented in a broad range of neoplastic tissues. STAT3 is a transcription factor that regulates the expression of numerous genes involved in the proliferation, survival, and metastasis of tumor cells. In addition, STAT3 contributes to tumorigenesis by modulating immune responses mediated by tumor stromal cells in the tumor microenvironment. The immuno-suppressive, pro-tumorigenic effects of STAT3 are regulated by induction or inhibition of several key cytokines. However STAT3 remains a difficult target to drug with conventional approaches. Here, we have studied the effects of selective downregulation of STAT3 in various cancer settings by optimized antisense oligonucleotides (ASOs). We assessed the effects of STAT3 downregulation on the expression of cytokines and the progression of cancer. Initially, the safety of inhibiting STAT3 was demonstrated in tolerability studies, where no notable toxicities were observed despite near complete abrogation of STAT3 expression in the liver following systemic delivery of ASO in both rodents and in non-human primate. ASO treatment led to STAT3 inhibition in tumor cells and several non-tumor stromal cell populations of the tumor. In addition, dramatic reduction in key pro-tumorigenic cytokines including IL-6 and IL-1b was observed in C26 colon cancer-bearing animals, which correlated with the decrease of STAT3 level in tumor and stromal cells. This result suggests that STAT3 might not only transmit the IL-6 signal from upstream pathway, but regulates IL-6 level possibly in an auto-feedback manner. Downregulation of STAT3 also led to the inhibition of IL-6-induced C-reactive protein (CRP) expression, which was recently reported to play a key role in the progression of multiple myeloma (MM). Moreover, inhibition of STAT3 resulted in a significant delay in tumor growth in STAT3-dependent MDA-MB-231 breast cancer and U251 glioblastoma xenograft models following systematic ASO treatment. The results from this study collectively suggest that STAT3 expression can be specifically modulated by ASOs in vivo tumor models and that in addition to effects in tumor cells STAT3 ASOs regulate the balance of tumorigenic cytokines in the tumor microenvironment. 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-302. doi:10.1158/1538-7445.AM2011-LB-302
HISTOPATHOLOGIC EVALUATION OF H3K27ME3 IS A PROGNOSTIC BIOMARKER FOR PEDIATRIC GLIOBLASTOMAS
Authors: A. R. Judkins, S. Venneti, M. Santi, M. M. Felicella, L. M. Sullivan, I. Dolgalev, D. Martinez, A. Perry, P. W. Lewis, D. C. Allis, C. B. Thompson
Journal: Neuro-Oncology (2014)

BACKGROUND: Up to 30% of pediatric glioblastomas (GB) demonstrate mutations in H3F3A, a gene variant encoding histone H3.3. Global reduction in H3K27me3 is associated with H3F3A K27M mutation. METHODS: We evaluated the utility of histopathological detection of this reduction in H3K27me3 as a prognostic biomarker. H3K27me3 expression was established by immunohistochemistry in 160 (118 pediatric and 42 adult) brain tumors of various subtypes and grades and 45 non-neoplastic reactive brain tissues. RESULTS: Global reduction in H3K27me3 was specific to GB cases with the H3F3A K27M mutantion, and was not observed in all other cases examined. In addition, H3F3A K27M mutant GB with reduced H3K27me3 exhibited a poor prognosis compared to H3F3A wild type tumors with preserved H3K27me3 (Log-rank (Mantel-Cox) test hazards ratio = 2.9, p = 0.0021). CONCLUSIONS: Global reduction in H3K27me3 is a histopathologically detectable surrogate for H3F3A K27M mutant GB that defines a poor prognosis subset of pediatric GB. SECONDARY CATEGORY: Pediatrics.
Osmotic Diuresis Due to Retained Urea after Release of Obstructive Uropathy
Authors: John F. Maher, George E. Schreiner, T. James Waters
Journal: New England Journal of Medicine (1963)

POLYURIA after the release of obstructive uropathy is a clinical entity of considerable medical interest. The prompt restoration of effective glomerular filtration may be associated with a delayed recovery of tubular function resulting in exaggerated polyuria. Both salt-losing nephritis and nephrogenic diabetes insipidus have been described.1 , 2 We have encountered a clinical case of massive diuresis that followed release of urinary-tract obstruction in which urea was proved to be the osmotic driving force. The observation is noteworthy because identification of the type of diuresis carries specific therapeutic implications.Case ReportAn 80-year-old man was admitted to the hospital because of syncope. . . .
Intra-abdominal Splenosis Mimicking Massive Gastrointestinal Bleeding
Authors: AYSE MAVI, BERNA DEGIRMENCI, RECEP BEKIS, HATICE DURAK
Journal: Clinical Nuclear Medicine (2003)

MAVI, AYSE M.D.; DEGIRMENCI, BERNA M.D.; BEKIS, RECEP M.D.; DURAK, HATICE M.D. Author Information
AB0501 Efficacy and safety of certolizumab pegol (CZP) with concomitant methotrexate (MTX) in korean rheumatoid arthritis (RA) patients (PTS) with an inadequate response to MTX
Authors: Y.M. Kang, W. Park, Y.E. Park, J.Y. Choe, S.-C. Bae, C.S. Cho, S.C. Shim, S.K. Lee, C.-H. Suh, H.-S. Cha, Y.W. Song, B. You, S.S. Lee, S.H. Lee, M.C. Park
Journal: Annals of the Rheumatic Diseases (2013)

Background CZP as a concomitant therapy to MTX has shown rapid and sustained efficacy in RA pts in previous international clinical trials. Objectives To confirm the efficacy and safety of CZP+MTX in Korean pts with active RA and an inadequate response to MTX. Methods In this 24-week (Wk), double-blind, randomised, placebo (PBO)-controlled study, pts with active RA (≥9 tender/swollen joints, CRP >15 mg/L or ESR ≥30 mm/h) were randomised 2:1 to receive CZP (initial dose of 400mg at Wks 0, 2 and 4 followed by 200mg every 2 Wks) or PBO. Pts remained on stable dose MTX. Pts with no ACR20 response at both Wks 12 and 14 were withdrawn. Primary efficacy endpoint was ACR20 response at Wk 24. Secondary outcomes included ACR20 at Wk 12, ACR50/70 at Wks 12 and 24, change from baseline (CFB) in HAQ-DI at Wk 24 and safety. LOCF was used to impute missing values for the efficacy endpoints. Results 121 pts (CZP N=81; PBO N=40) were included in efficacy analyses (mean disease duration=6.2yrs, mean DAS28[ESR]=7.4). Baseline characteristics were comparable between the 2 groups. The min-max MTX dose was 10-20 mg/Wk. ACR20 was significantly higher in the CZP vs PBO group at Wk 1 (P=0.013). This was maintained to Wk 24 (66.7% vs 27.5% P<0.001; figure). ACR50/70 responses were significantly higher in the CZP vs PBO groups at Wk 24 (figure). HAQ-DI, pain and global disease activity significantly improved in the CZP vs PBO groups at Wk 24. Mean CFB was -0.56 vs -0.14 for HAQ-DI (P<0.001), -28.9 vs -9.6 for pain (P<0.001), and -25.3 vs -13.5 for global disease activity (P=0.009). AEs were reported in 65.9% of CZP and 57.1% of PBO pts; none had a fatal outcome. The most common AEs in CZP pts were upper respiratory tract infections (25.9%) and abdominal pain (5.9%). SAEs were reported in 9.4% of CZP pts, including infections in 6pts, of which 2 had TB (background rate=88/100,000 persons).1 No SAEs were reported in the PBO group. ![Figure][1]</img> Conclusions CZP 200mg+MTX resulted in a rapid and sustained reduction in RA signs and symptoms, and improved physical function and pain compared with PBO+MTX. CZP had an acceptable safety profile. This confirms the efficacy and safety of CZP in MTX refractory RA. 1. Dye et al. PLoS One. 2011; 6(6): e21161. Disclosure of Interest None Declared [1]: pending:yes
P228 HEPATITIS C VIRUS NS5A PROTEIN TRIGGERS OXIDATIVE STRESS BY INDUCING NADPH OXIDASES 1 AND 4 AND CYTOCHROME P450 2E1
Authors: O.A. Smirnova, O.N. Ivanova, F. Mukhtarov, B. Bartosch, S.N. Kochetkov, A.V. Ivanov
Journal: Journal of Hepatology (2014)
Tips for a Physician in Getting the Right Job, Part VII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2013)

In addition to general interview questions, the applicant for an administrative position may be asked behavioral questions. It is possible to prepare for behavioral interview questions partly through research to find out what the employer wants and then doing a self-inventory to determine what can best illustrate that the candidate has those attributes. It is also helpful to review likely questions and to rehearse the answers. Many behavioral questions, several of which have hints regarding the answers, are included in this article.
MTOR KINASE INHIBITORS AND APOPTOSIS IN GLIOBLASTOMA
Authors: W. A. Weiss, R. Wong, Q.-W. Fan, S. Ilkhanizadeh, M. Lu, J. Beyer, N. Dube, J. Forsayeth, A. Kells, T. Xu, K. Bankiewicz, G. Ducker, M. Feldman, K. Shokat
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma represents the most common primary brain tumor, and among the most lethal of cancers. The axis linking receptor tyrosine kinases and phosphatidylinositol 3' kinase to the mammalian target of rapamycin (mTOR) is activated in a majority of glioblastomas, suggesting mTOR as a prominent target for therapy. A new class of mTOR kinase inhibitors already in clinical trials disrupts signaling through two mTORC1 translational effectors (S6K and eIF4E) whereas clinical allosteric binders (rapamycin and analogues) disrupt only S6K. METHODS: We tested three distinct mTOR kinase inhibitors (KU63794, PP242 and the clinical compound MLN128) against glioma cell lines and primary cultures wild-type or mutant at PTEN. We used viability assays, flow cytometry, western blotting, as well as convection enhanced delivery and gavage to test agents in glioblastoma. RESULTS: All agents blocked viability in a dose dependent manner. PP242 uniquely induced apoptosis. Cell based screening suggested Janus Kinase 2 (JAK2) and protein kinase C alpha (PKCa) as prominent off-targets for PP242. We validated both off-targets. To determine whether these targets contributed to apoptosis, we combined inhibition or knockdown of JAK2 and PKCa. Blocking both kinases drove apoptosis, associated with reduced phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3). Apoptosis was abrogated by inhibition of mTOR. The EGFR inhibitors erlotinib and lapatanib partially blocked PKC and JAK2. Combining either EGFR inhibitor with a JAK2 inhibitor also drove apoptosis in a PTEN-indepenent manner, associated with blockade of p-STAT3. Current experiments extend this combination in-vivo. CONCLUSIONS: We recently demonstrated that EGFR and EGFRvIII converge to activate STAT signaling in glioblastoma. By dissecting off-target effects underlying the ability of an mTOR kinase inhibitor to drive apoptosis, we identified a combination therapy approach that blocks STAT activation. Use of EGFR and of JAK kinases in combination blocked STAT signaling, and was associated with apoptosis in glioblastoma. Combined therapy with approved JAK and EGFR inhibitors could be translated rapidly to patients. SECONDARY CATEGORY: Tumor Biology.
Technetium-99m Tetrofosmin Uptake in Insular Thyroid Carcinoma
Authors: Berna Degirmenci, Aysel Aydin, Abdurrahman Comlekci, Ozhan Ozdogan, Recep Bekis
Journal: Clinical Nuclear Medicine (2003)

The authors describe a 42-year-old man with insular thyroid carcinoma. In this patient, iodine-131 (I-131) and technetium-99m (Tc-99m) tetrofosmin imaging were performed to investigate residual thyroid tissue and metastatic foci of tumor. Both I-131 and Tc-99m tetrofosmin images showed metastatic foci, but Tc-99m tetrofosmin imaging revealed the lesions better than did the I-131 scan. Tc-99m tetrofosmin imaging does not require withholding of thyroid hormone suppression and can be used for follow-up evaluation of patients with insular thyroid carcinoma.
Rectal Cancers: Our Experience at Hassan II University Hospital of Fez, Morocco
Authors: Lamiae Amaadour, Zineb Benbrahim, Rajae Najib, Adil Ibrahimi, Khaled Maazaz, Afaf Amarti, Khaled Hassouni, Siham Tizniti, Khaled ait Taleb, Samia Arifi, Nawfel Mellas, Omar El Mesbahi
Journal: Annals of Oncology (2013)
Abstract 694: Characterization of a novel monoclonal antibody to Glia maturation factor-beta showing significant clinical utility in the identification of breast carcinoma
Authors: Ozgul M. Alper, Cui P. Chen, Achille Akoa, Marille Herrmann, Ozge Alper
Journal: Cancer Research (2012)

Abstract Background: Glia maturation factor beta (GMF-beta) is a growth and differentiation factor of brain cells, stimulation of neural degeneration and inhibition of proliferation of tumor cells. It was recently found to involve in the progression of serous ovarian carcinoma. In the present study, we generated a novel antibody against human GMF-beta and investigated the potential of GMF-beta as a biomarker in breast cancer. Methods and findings: We generated a novel monoclonal antibody (mAb), AB-GMF-beta using hybridoma technology and native protein as an immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human GMF-beta protein and displayed high affinity as assessed by ELISA, immunohistochemistry assay, western blot and flow cytometry applications. Using this mAb in competitive ELISA, we showed for the first time that soluble GMF-beta level is significantly increased in metastatic breast cancer patients’ plasma which directly correlated with GMF-beta expression pattern in metastatic breast cancer tissues. Tissue expression of GMF-beta was determined by using immunohistochemical techniques. Seventy normal and 241 breast cancer tissues were included which consist of 194 ductal and 47 lobular carcinoma samples. Most of normal tissues showed negative or weak nuclear staining, while different levels of nuclear, and diffuse and weak cytoplasmic staining were observed in cancer sections. To evaluate the immunoreactivity of GMF-beta associated with tumor histological types, the staining intensity in nucleus were scored as 0, 1+, 2+ and 3+. Grade 0 and 1+ were defined as negative and 2+ and 3+ as positive. Forty four percent of ductal carcinomas showed strong staining whereas it is significantly increased to 72.3% in lobular tumors (p&amp;lt;0.001). Conclusion: The novel AB-GMF-beta mAb showed high performance in blood and tissue assays. The circulating GMF-beta levels and expressions in breast tissues are significantly increased in breast cancer patients in comparison of normal controls. The increased tissue expressions in breast carcinoma associate with histological tumor types. Our data suggest the potential clinical use of GMF-beta as a biomarker for diagnosis and prognosis in blood and tissue as well as a therapeutic target. 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 694. doi:1538-7445.AM2012-694
A1.46 CD8<sup>+</sup>T cell profiles in patients with rheumatoid arthritis and their relation with disease activity
Authors: Helena Carvalheiro, Cátia Duarte, Sandra Silva-Cardoso, José A P da Silva, M Margarida Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> CD8<sup>+</sup>T cells are known to be present in the synovial fluid and synovium of rheumatoid arthritis. However, their role in the disease pathogenesis remains largely unexplored. This work intended to characterise blood and synovial fluid CD8<sup>+</sup>T cell functional subsets found in patients with rheumatoid arthritis and explore their importance in regulating the activity of the disease. <h3>Methods</h3> The functional phenotypes of CD8<sup>+</sup>T cells were determined in seventy-eight patients with rheumatoid arthritis (forty-four in remission (DAS28 &lt; 2.6), thirty-four with active disease (DAS28 &gt; 3.2)) and the results were compared to those of sixty-four sex and age-matched healthy controls (HC). Ten paired samples of blood and synovial fluid (SF) from patients with active disease were also analysed, and the expression of surface markers, cytokines and proteolytic enzymes of CD8<sup>+</sup>T cells were determined. <h3>Results</h3> Data shows that peripheral blood CD8<sup>+</sup>T cells from both patients with active disease and in remission present an activated phenotype with a marked pro-inflammatory profile. Remission is associated with a lower production of proinflammatory mediators, such as IL-6 and IFNγ, but the changes in cell subsets observed in active disease persist or are even accentuated, with the frequency of the central memory CD27<sup>+</sup>CD62L<sup>+</sup>CCR7<sup>+</sup>CD8<sup>+</sup>T cells significantly reduced, and the short-term effector CD27<sup>-</sup>CD62L<sup>-</sup>CD8<sup>+</sup>and the activated subset CD69<sup>+</sup>CD8<sup>+</sup> T cell subsets significantly increased when compared to healthy controls. The CD8<sup>+</sup>T cells present in the SF of active RA present a more exacerbated effector memory (CD27<sup>+</sup>CD62L<sup>-</sup>) and activated (CD25<sup>+</sup>and CD69<sup>+</sup>) CD8<sup>+</sup>T cell phenotype than the ones in the paired blood samples. Finally, we report that the production of cytokines by CD8<sup>+</sup>T cells from the synovial fluid is correlated with that observed in peripheral blood samples, with increased production of proinflammatory cytokines such as IL-6 and TNFα. <h3>Conclusions</h3> Our data demonstrate major shifts in CD8<sup>+</sup>T cells subsets and in their cytokine production in rheumatoid arthritis, which are related to disease activity. This suggests that these cells play relevant roles in the pathogenesis of the disease.
Abstract 4062: Human peptide deformylase expression and activity in various cancers
Authors: Katie M. Reindl, Karly Sorensen
Journal: Cancer Research (2010)

Abstract Human peptide deformylase (hsPDF) expression has been detected in human cells, but it is unclear if the enzyme is functional. Our hypothesis is that hsPDF is functional in human cells. The objectives of this study were to 1) quantify hsPDF transcript levels in normal and cancerous cells and tissues and 2) determine the effects of hsPDF inhibition on the proliferation of normal and cancerous cells. Quantitative real-time PCR was used to measure hsPDF mRNA levels in normal and cancerous cell lines and tissues. Increases in hsPDF mRNA expression were seen in most cancer cell lines compared to the normal. hsPDF was up-regulated in most, but not all, cancer tissues compared to the normal, with the greatest differences observed in breast, colon, and lung tissues. Various cancer and normal cell lines were treated with increasing concentrations of a known PDF inhibitor, actinonin, and cell proliferation was assessed. The antiproliferative effects of actinonin were greater in prostate, colon, and breast cancer cell lines than in the normal cell lines. These results suggest that hsPDF is up-regulated in certain cancers, and that it may play an active role in the proliferation of human cells. 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 4062.
Endoscopic ultrasound-guided drainage of giant liver abscess associated with transgastric migration of a self-expandable metallic stent
Authors: B. Medrado, F. Carneiro, T. Vilaça, T. Gouveia, M. Frazão, E. de Moura, P. Sakai, J. Otoch, E. Artifon
Journal: Endoscopy (2013)

Liver abscesses are usually drained percutaneously and if drainage is inadequate, surgery may be necessary [1]. Successful endoscopic ultrasound (EUS)-guided drainage has been described for abscesses located in the pancreas, pelvis, liver, and subphrenic space [2] [3] [4]. We report the first case of EUS-guided drainage of an abscess in the left lobe of liver in a patient with pancreatic tumor, using a self-expanding metallic stent (SEMS).