tbuckley/cabot-search huggingface dataset:
P2-01-26: TIMPv: a novel downstream transcriptional target gene that underpins CD146-suppressed breast tumor invasion
Authors: A Ouhtit, Z Abdelmageed, A Fernando, RL Gaur, MHG Raj
Journal: Cancer Research (2011)

Abstract Background: CD146, a marker of endothelial cells, promotes tumor progression of many cancers including melanoma and prostate. Strikingly, several lines of evidence suggest that it is a suppressor of breast cancer (BC) progression. Not only the ligand(s) has not been identified, but CD146-downstream signaling mechanisms remain unknown. Material and Methods: Here, we report the functional importance of CD146 and that of a novel transcriptional target of CD146-signaling, variant of tissue inhibitor of metalloproteinases (TIMPv) identified by microarray analysis, in underpinning the suppression of BC invasion, using novel validated Enhanced Green Fluorescent Protein (EGFP)-inducible systems of CD146 expression both in vitro and in vivo. Results: In functional experiments, induction of CD146 inhibited BC cell migration and invasion. TIMPv was identified by expression profiling as a novel transcriptional target of CD146-signaling, an association validated by quantitative PCR and immunoblotting experiments in a range of breast and melanoma cancer cells. However, siRNA inhibition of CD146 in the SKMel-28 melanoma cell line increased TIMPv expression, suggesting that while TIMPv is a positive transcriptional target of CD146 in BC cells, it is negatively regulated in melanoma cells. Furthermore, the functional relevance of TIMPv to CD146-suppressed metastasis was demonstrated by selective suppression of TIMPv in CD146-expressing BC inducible cells using RNAi. More interestingly, induction of CD146 expression in vivo using mouse EGFP-inducible system of CD146 expression resulted in suppression of breast tumor growth. Discussion: Our study is the first report to provide a functional molecular link of TIMPv to cancer via unique axis that underpin CD146-suppressed BC progression, thus identifying TIMPv as a potential target for guiding the development of novel therapeutic strategies for BC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-26.
AB0689 Comparison of pvas scores with mra findings of continued activity in singaporean children with takayasu arteritis
Authors: L. Das, S. F. Hoh, J. Tan, T. Arkachaisri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Disease activity assessment in childhood Takayasu Arteritis (cTA) is an ongoing issue. Recently a new index of disease activity Pediatric Vasculitis Assessment Score (PVAS) was validated for children. <h3>Objectives</h3> Our aim was to compare disease activity scoring utilizing the PVAS, to imaging features indicating ongoing inflammation in our small cohort of pediatric Takayasu arteritis patients, at onset and at follow up. <h3>Methods</h3> Case notes of children fulfilling the EULAR vasculitis classification criteria for cTA were assessed from the initial rheumatology consultation and the visit corresponding to the last MRA. PVAS scores were calculated. MRA reports were assessed for imaging features indicating disease activity i.e. wall contrast enhancement and irregularity. Descriptive statistics (median, interquartile range (IQR) &amp; percentiles) were used to describe the data. <h3>Results</h3> Patients #1 &amp; 2 presented with acute stroke and Patients #3 &amp; 4 with hypertension. Patient#5 was referred 20 months after diagnosis but had never received immunosuppression. Median age of onset was 11 years (IQR 7.8-11.9) and median time for follow up was 13 months (IQR 8-15). 80% had MRA progression with further vessel involvement and continued wall enhancement. 40% of patients initially only had branch involvement +/- renal artery stenosis but later developed aortic involvement. ESR was elevated on follow up in 40%. <h3>Conclusions</h3> In this small cohort of cTA patients, follow up PVAS did not reflect MRA findings of continued disease activity in 4 out of 5 patients. Further studies in larger cohorts are necessary to further characterize this issue and this is ongoing in our region. <h3>References</h3> Dolezalova P, Price-Kuehne FE, Özen S <i>et al.</i>: Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS). Ann Rheum Dis 2012;00:1–6. Andrews J, Mason JC <i>et al.</i>: Takayasu’s arteritis—recent advances in imaging offer promise. Rheumatology 2007;46:6–15 <h3>Disclosure of Interest</h3> None Declared
Obscure gastrointestinal bleeding due to small-bowel phlebectasias
Authors: Carolina Olano, Pablo Machado, Joaquín Berrueta, Verónica Irisarri
Journal: Endoscopy (2014)

Phlebectasias or venous ectasias are rare benign vascular abnormalities of the gastrointestinal tract [1]. They are vascular "malformations" with an abnormal endothelial lining and are thought to be congenital in origin, although the causes and etiological factors responsible for their occurrence are not clear. The lesions are usually asymptomatic; however, occasionally, they may present with gastrointestinal hemorrhage, varying from mild to massive. On endoscopy the lesions appear as bluish submucosal lesions, with a nodular, polypoid, or rarely tumor-like appearance [2].
Germline<i>HABP2</i>Mutation Causing Familial Nonmedullary Thyroid Cancer
Authors: Sudheer Kumar Gara, Li Jia, Maria J. Merino, Sunita K. Agarwal, Lisa Zhang, Maggie Cam, Dhaval Patel, Electron Kebebew
Journal: New England Journal of Medicine (2015)

Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.
Abstract 3136: C-Myc-mediated transcriptional repression of HPP1 in colon cancer by recruitment of HDACs
Authors: Jian Wang, Elahi Abul, Jonathan Hernandez, Whalen Clark, Alex Achille, Jihui Hao, Ed Seto, David Shibata
Journal: Cancer Research (2012)

Abstract Background: Epigenetic gene silencing plays a critical role in tumorigenesis. HPP1, a putative tumor suppressor gene is downregulated in a number of tumor types including colon cancer. As a mechanism of suppression, promoter hypermethylation of HPP1 is known to be important, however the contributions and mechanisms of histone deacetylation have not been described. Additionally, the c-myc oncogene also contributes to the suppression of HPP1 via promoter binding to a cognate E-box site. We sought to elucidate the role of histone deacetylation and the potential interplay with c-myc in the transcriptional regulation of HPP1. Methods: The HPP1 non-expressing cell lines, HCT-116 and DLD-1, were treated with the DNA methylation inhibitor, 5-aza-2′-deoxycitidine (5-Aza-DC) and/or histone deacetylation (HDAC) inhibitors, including sodium butyrate (SB), Vorinostat (SAHA), trichostatin A (TSA) and valproic acid (VPA). Knockdowns of c-Myc and HDAC-1, 2, 3 and 4 were performed using siRNA. Protein and mRNA expression of HPP1 were determined by Western Blot and RT-PCR respectively. Furthermore, Chromatin immunoprecipitation (ChIP) and ChIP-re-ChIP experiments were used to demonstrate the binding of c-Myc and HDACs to the HPP1 promoter. Co-IP assays were used to test the physical interaction between c-Myc and HDAC3. After knockdown of HDAC3 using siRNA in HCT116, ChIP was also used to test the activity of acetylated histone 4 (AcH4). Results: 5-Aza-DC as well as HDAC inhibitors, including SB, TSA, SAHA and VPA, resulted in the re-expression of HPP1 in HCT-116 and DLD-1 cells. Individual HDAC inhibitors administered in combination with 5-Aza-DC resulted in a synergistic effect on HPP1 re-expression. Concordantly, knockdown of HDAC2 and HDAC3 in HCT116 cells, and HDAC1 and HDAC3 in DLD-1 cells by siRNA significantly enhanced HPP1 expression. Co-IP, ChIP and double ChIP experiments confirmed binding of c-myc to the HPP1 promoter as a complex with dominant recruitment of HDAC3. By ChIP assay, the levels of AcH4 increased significantly in HCT116 after knockdown of HDAC3. Conclusions: We have demonstrated that HDAC-1, -2 and -3 contribute to the epigenetic regulation of HPP1. Moreover, c-myc binds to the HPP1 promoter and mediates epigenetic suppression via the dominant recruitment of HDAC3 with subsequent enhancement of histone deacetylation. Our findings may lead to a greater biologic understanding for the application of the targeted use of HDAC inhibitors for anti-cancer therapy. 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 3136. doi:1538-7445.AM2012-3136
Influence of Age on Induction of Mammary Tumors by Diethylstilbestrol in C3H/HeN Mice With Low Murine Mammary Tumor Virus Titer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D L Greenman, B Highman, J J Chen, G J Schieferstein, M J Norvell
Journal: JNCI Journal of the National Cancer Institute (1986)

C3H/HeN female mice with low murine mammary tumor virus titer (MTV-) were fed diets containing a targeted concentration of 640 ppb diethylstilbestrol [(DES) CAS: 56-53-1; 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-phenol]. Mice were started on DES at 3, 5, 7, or 9 weeks of age. Some continued on the diet throughout the rest of their life-spans, whereas others were killed as soon as they had been fed DES for 2, 4, 6, 8, 10, or 12 weeks. Controls were also examined throughout the study. Among mice killed early, the only observation significantly influenced by age at the start of DES treatment was the presence or absence of corpora lutea (CL). DES did not prevent CL from appearing in mice started on DES at 7 or 9 weeks of age, but it did prevent their appearance in about 25% of the mice started at 5 weeks and in up to 75% of the mice started at 3 weeks of age. In the life-span-exposure groups, CL either disappeared or were never formed in 88% or more of the mice, regardless of age at the start of treatment. Neoplastic or presumptive preneoplastic lesions apparently influenced by DES in the life-span-treatment groups included ovarian tubular adenomas; granulosa cell tumors and luteomas; pituitary cystoid degeneration, hyperplasia, and adenomas; uterine adenocarcinomas and cervical adenosis; mesotheliomas; and mammary hyperplastic alveolar nodules (HANs) and adenocarcinomas. Luteoma and granulosa cell tumor incidences were reduced by DES, regardless of age at the start of treatment. Influence of age at the start of treatment was minimal or not apparent for mesotheliomas, uterine adenocarcinomas, or pituitary adenomas; however, pituitary cystoid degeneration and hyperplasia and cervical adenosis occurred in higher frequency and/or with shorter duration of DES exposure the earlier that treatment was started. A delay in the start of DES treatment was associated with a remarkable delay in HAN and mammary adenocarcinoma development. This was especially apparent in young mice (3-7 wk old) in which a 2-week delay in treatment resulted in a 20-week delay in HAN or tumor onset. Age at the start of treatment was a major factor in susceptibility of C3H/HeN-MTV- female mice to DES-induced mammary tumorigenesis.
A Randomized Clinical Trial of Granulocyte Transfusions for Infection in Acute Leukemia
Authors: Jane B. Alavi, Richard K. Root, Isaac Djerassi, Audrey E. Evans, Stephen J. Gluckman, Rob Roy MacGregor, DuPont Guerry, Alan D. Schreiber, John M. Shaw, Penelope Koch, Richard A. Cooper
Journal: New England Journal of Medicine (1977)

In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.
Primary Bilateral Adrenal Involvement of Non-Hodgkin’s Lymphoma Shown on a Ga-67 Citrate Scan
Authors: EIKO YAMASHITA, TOSHIKI KOBAYASHI, YUTAKA SUZUKI
Journal: Clinical Nuclear Medicine (2000)

Primary adrenal non-Hodgkin’s lymphoma is rare. The authors describe a 62-year-old woman with bilateral adrenal non-Hodgkin’s lymphoma that was found incidentally. Several serum enzymes were monitored, but only the lactate dehydrogenase level was elevated. Computed tomographic and magnetic resonance scans showed nonspecific features of bilateral adrenal tumors with slight enhancement. The Ga-67 citrate scan revealed localized and intense accumulation in the posterior aspect of the upper abdomen bilaterally. After tumor resection, the lymphoma was diagnosed as a diffuse large-cell type.
THE RATIO OF CONTRAST MEDIA VOLUME TO THE ESTIMATED GLOMERULAR FILTRATION RATE AND SYNTAX SCORE PREDICT 3-YEAR POOR OUTCOME IN PATIENTS WITH ACUTE CORONARY SYNDROME AND CHRONIC KIDNEY DISEASE UNDERGOING EMERGENCY CORONARY PROCEDURE
Authors: Tatsuhisa Ozaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masashi Ishimi, Hideyuki Hakui, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2016)
SERIAL ANGIOGRAPHIC FOLLOW-UP AT 6 AND 18 MONTHS AFTER IMPLANTATION OF THE NOVEL NOVOLIMUS-ELUTING BIORESORBABLE VASCULAR SCAFFOLD SYSTEM FOR THE TREATMENT OF SINGLE DE NOVO CORONARY LESIONS: A SUBANALYSIS OF THE DESOLVE NX CLINICAL TRIAL
Authors: Ricardo A. Costa, Alexandre Abizaid, Jose de Ribamar Costa, Daniel Chamié, Andrea Abizaid, Rodolfo Staico, Juliana Castro, John Yan, Vinayak Bhat, Lynn Morrison, Sar Toyloy, Stefan Verheye, Amanda Sousa
Journal: Journal of the American College of Cardiology (2015)
Cost-effectiveness analysis of endoscopic ultrasound as a first-line staging tool for patients with non-small-cell lung cancer
Authors: L Lai
Journal: Endoscopy (2011)

There was little data on the cost-effectiveness of endoscopic ultrasonography with fine-needle-aspiration (EUS-FNA) as the first-line staging tool for non-small-cell-lung-cancer (NSCLC), especially when compared with the gold standard mediastinoscopy.
National Cancer Program Created Network for Delivering Research Results
Authors: Patricia A. Newman, Michael E. Newman
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article National Cancer Program Created Network for Delivering Research Results Get access Patricia A. Newman, Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael E. Newman Michael E. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 319–321, https://doi.org/10.1093/jnci/83.5.319 Published: 06 March 1991
Abstract 3661: The impact of tumor-infiltrating natural killer cells on ovarian cancer progression
Authors: Ahmed El-gazzar, Eva Eckelhart, Paul Perco, Reinhard Horvat, Veronika Sexl, Michael Krainer
Journal: Cancer Research (2011)

Abstract Cancers adopt diverse strategies to safeguard their survival by evading tumor surveillance. Natural killer (NK) cells and CD8 T-lymphocytes are capable of destroying tumor cells thus playing a critical role in tumor immunity. In previous studies, we showed that NK cell derived TRAIL is essential for the cytotoxic activity of the DR5 agonistic antibody AD5-10, since depletion of NK cells abolished the antitumor activity of AD5-10 in a xenograft ovarian cancer (OC) mouse model. In the present study, we investigated whether NK cells are associated with clinical outcome as well as with the immune infiltrate showing anti-tumor immunity in OC. We analyzed NK cell infiltration in human primary ovarian tumor tissues using immunohistochemical analysis of a representative population of OC patients on a tissue microarray. NK tumor-infiltrating cells were detected within tumor tissues, whereas CD3 tumor-infiltrating T-lymphocytes were almost undetectable. NK cells in addition inversely correlated with FIGO stage (r=−0.51, p&amp;lt;0.001) and tumor grade (r=−0.3, p=0.03). These data indicate that the presence of intratumoral NK cells correlates with improved clinical outcome in OC. When we analyzed the cytotoxic capacity of human NK cells against OC cells in vitro, we found that human NK cells were capable to induce apoptosis in a concentration-and time-dependent manner in several OC cell lines. Interestingly, the addition of the DR5 agonistic antibody AD5-10 sensitized TRAIL resistant OC cell lines to NK cells mediated cytolysis. To study tumor surveillance of OC in vivo, we are currently setting up mouse models. Transformed murine ovarian surface epithelial (MOSE) cell lines derived from C57BL/6 mice have been implanted intraperitoneally into syngenic wild type, RAG2 -/-, RAG2 -/- γ -/-, NK depleted, CD8 depleted C57BL/6 recipient mice. The outcome of these studies will be presented. In summary, our findings point at a critical role for NK cell mediated tumor surveillance for OC development. Importantly, NK cell infiltration correlates with prognosis in human ovarian carcinoma. Thus, our study may open novel therapeutic opportunities by interfering with host immunity in the future. 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 3661. doi:10.1158/1538-7445.AM2011-3661
AB0139 Active vitamin D hormone antagonizes age-induced functional alterations in human osteoblasts
Authors: P. Oelzner, S. Franke, G. Hofmann, G. Wolf
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increased production and accumulation of advanced glycation endproducts (AGEs) in chronic inflammatory diseases such as rheumatoid arthritis (RA) and during physiological aging may contribute to osteoporosis by suppression of bone formation. On the other hand, RA and older age are frequently associated with vitamin D deficiency. In contrast to the suppressive effects of AGEs on osteoblast (OB) proliferation, the active vitamin D metabolite 1.25-dihydroxyvitamin D3 (1,25D3) stimulates OB proliferation and bone formation. <h3>Objectives</h3> The aim of our study was to investigate if 1,25D3 is able to prevent AGE-induced functional alterations of OB. <h3>Methods</h3> Human OB were isolated and cultured from bone tissue of 10 patients with knee osteoarthritis and joint replacement. Cells from passages 3 - 7 were treated for 48 hours with control bovine serum albumin (Co-BSA), AGE-BSA and AGE-BSA+1,25D3, respectively (medium concentrations: 5 mg/ml AGE-BSA and Co-BSA, respectively; 100 pmol/l and 500 pmol/l 1,25D3). MRNA and protein expression of bone alkaline phosphatase (bALP), collagen type 1 (Col1) and osteocalcin (OC) were investigated by qRT-PCR and Western Blot-analysis, respectively. For measurement of proliferation and vitality BrdU- and MTT assays were used, respectively. <h3>Results</h3> In comparison with control-BSA (mRNA expression 100%) the treatment with AGE-BSA led to a significant reduction of relative mRNA expression of bALP (77±5%; p&lt;0.05), Col 1 (58±35%; p&lt;0.05) und OC (67±24%; p&lt;0.05). The co-treatment with 1,25D3 resulted in a complete inhibition of the AGE-BSA induced suppression of mRNA-expression. The relative mRNA expression after co-treatment with 100 pmol/l and 500 pmol/l 1,25D3 was significantly higher (p&lt;0.05) in comparison with the AGE-BSA-treated OB (115±11% and 126±15% for bALP, 100±15% and 152±51% for Col1 and 4243±269% and 6121±2789% for OC, respectively). Furthermore, the relative mRNA expression of OC was significantly higher in comparison to control-BSA-treated OB after co-treatment with both 1,25D3 concentrations. Corresponding results were observed for protein expression. <h3>Conclusions</h3> The results of the investigations indicate the ability of active vitamin D hormone to antagonize completely suppressive effects of AGEs on selective functions of OB in vitro. 25-hydroxyvitamin D3 can be metabolized into active vitamin D hormone in OB. Therefore, in diseases with both AGE accumulation and a high frequency of vitamin D deficiency such as RA both factors may contribute to potentiation of suppressive effects on bone formation and bone repair. With respect to bone formation, a sufficient vitamin D substitution may be of particular importance in RA and in older age. <h3>Disclosure of Interest</h3> None Declared