tbuckley/cabot-search huggingface dataset:
Abstract 151: Advancing pathway analysis using bioluminescent reporters
Authors: Matthew B. Robers, Brock Binkowski, Natasha Karassina, Pete Stecha, Chris Eggers, Jey Cheng, Kris Zimmerman, Frank Fan, Mei Cong
Journal: Cancer Research (2012)

Abstract To enable investigation of key cellular signaling pathways, Promega has developed a portfolio of bioluminescent reporter gene assays using Firefly and Renilla luciferases. In combination with best-in-class luciferase detection reagents, these genetic reporter systems enable interrogation of important cellular responses involved in cancer, inflammation, and CNS disease. To address specialized customer needs in our industrial and research markets, Promega has a new custom assay service team dedicated to applying these enabling technologies through strategic external research collaborations. The performance of this technology portfolio is presented, including novel applications of luciferase reporters to interrogation of cytokine, stress, and toxicity pathway responses. 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 151. doi:1538-7445.AM2012-151
Abstract 1939: Association between LRRK2 and 4E-BP1 protein levels in normal and malignant cells
Authors: Berta Pons, Gemma Armengol, Santiago J. Ramón y Cajal
Journal: Cancer Research (2011)

Abstract Translational control is a crucial component of cancer development and progression. Eukaryotic initiation factor 4E (eIF4E) mediates eIF4F association with the mRNA 5’ cap structure to stimulate cap-dependent translation initiation. The eIF4E-binding protein, 4E-BP1, regulates cap-dependent translation through its phosphorylation at multiple sites. The search for new kinases that could be implicated in 4E-BP1 phosphorylation, and determination of the mechanisms that affect 4E-BP1 stability are important to understand the role of eIF4E in cell transformation. In this study, we investigate 48 kinases that may be implicated in 4E-BP1 phosphorylation and stability. The screening study was based on analysis of 4E-BP1 status after inhibition of these kinases in a breast carcinoma cell line (MDA-MB 231 cells). With the use of this method, several kinases that affect 4E-BP1 stability (LRRK2, RAF-1, p38γ, GSK3β, AMPKα, PRKACA and PRKACB) and 4E-BP1 phosphorylation (CDK1, PDK1, SRC, PRKCB1, PAK2, p38β PRKCA and CaMKKB) were identified. These novel findings provide evidence that 4E-BP1 can be regulated and stabilized by multiple kinases implicated in several cell signaling pathways. We also found that LRRK2 downregulation affects 4E-BP1 stability and causes degradation of this factor in various cell types. Interestingly, inhibition of proteasome activity by MG132 restored total 4E-BP1 protein levels in cells where LRRK2 was downregulated. In addition, these stabilization events appear to be functionally important for cell growth control in normal cells. 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 1939. doi:10.1158/1538-7445.AM2011-1939
Abstract 1586: Oral administration of HIV-protease inhibitors reduces ovarian tumor growth in vivo
Authors: Natalie A. Vandeven, Lijun Tan, Dorothy Sorenson, J. Rebecca Liu
Journal: Cancer Research (2011)

Abstract INTRODUCTION: Ritonavir boosted lopinavir (LPV/r) is an FDA approved HIV-protease inhibitor combination that is a well tolerated and preferred treatment for HIV patients. Ritonavir is a potent irreversible inhibitor of cytochrome P450 isoform 3A (CYP3A) which can substantially increase bioavailability of lopinavir in vivo. This combination of lopinavir and ritonavir has been shown to increase the efficacy of reducing viral load in AIDS patients. HIV patients taking antiretroviral protease inhibitors such as LPV/r have a lower incidence of HIV associated malignancies such as non-Hodgkin's lymphoma, cervical cancer and Kaposi's sarcoma, leading to the hypothesis that these drugs have antineoplastic activity. Given the need for novel treatment approaches in ovarian cancer, we are investigating the antineoplastic effects of LPV/r, in vivo. METHODS: A xenograph model of ovarian cancer is used to assess the antineoplastic effect of LPV/r in vivo. Oral doses of LPV/r dissolved in corn oil are administered to mice over the course of 2-3 weeks. Tumor area and mouse weight are monitored. After 2-3 weeks tumors are harvested and analyzed. RESULTS: Preliminary results indicate that LPV/r administered orally in combination with a high fat diet inhibits tumor growth in vivo without inducing weight loss. In contrast, the dose of intraperitoneal cisplatin required to attain a similar antineoplastic effect resulted in significant weight loss and morbidity. CONCLUSIONS: Because protease inhibitors can induce both apoptotic and non-apoptotic ovarian cancer cell death in vitro and in vivo, these drugs may circumvent chemoresistance due to alterations in apoptotic response. Our data suggests that LPV/r may also have clinical application in the treatment of ovarian cancer. 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 1586. doi:10.1158/1538-7445.AM2011-1586
Abstract 1998: Inhibition of hedgehog signaling in prostate cancer by extracts of Sutherlandia
Authors: Glenn A. Jackson, Hui Lin, Yuan Lu, Sara K. Drenkhahn, Nicholas J. E. Starkey, Christal D. Huber, Wei Lei, George E. Rottinghaus, William Folk, Jim D. Browning, Cindy L. Besch-Williford, Kevin L. Fritsche, Dennis B. Lubahn
Journal: Cancer Research (2012)

Abstract Prostate cancer possesses long latency periods and is responsive to dietary mediators, making it a target for phytochemoprevention. Many botanical compounds that have been proposed to prevent cancer may potentially work via inhibition of the hedgehog signaling pathway. Here we investigated the potential of Sutherlandia frutescens (also called Lessertia and “cancer bush” in South Africa) to inhibit hedgehog signaling. We hypothesize that the anti-cancer effects of Sutherlandia are due to its inhibition of hedgehog signaling pathway activity. Methods: We evaluated Sutherlandia's effects of growth inhibition in vitro both in the human prostate cancer cell line PC3 and mouse prostate cancer cell line TRAMP-C2 by exposing the cells for 72hrs to plant extracts before protein concentrations were measured to evaluate inhibition of growth. To determine hedgehog pathway inhibitory activity, we treated two different cell lines (an NIH3T3 cell line and a TRAMPC2 cell line) stably transfected with a firefly luciferase reporter having Gli response elements in the firefly luciferase promoter. After 48hr exposure to treatment with multiple doses of Sutherlandia, a firefly substrate was added to the cell lysate and the luciferase signal was measured using a Biotek Synergy plate reader. Finally, Sutherlandia was incorporated into a diet and fed to TRAMP (Transgenic Adenocarcinoma Mouse Prostate) mice to examine whether the plant can delay or even inhibit prostate cancer incidence in the TRAMPmouse model. Results: Sutherlandia extracts inhibited growth of both PC3 and TRAMPC2 cells. In addition, hedgehog signaling was inhibited by Sutherlandia in both NIH3T3 and TRAMPC2 reporter cells. Interestingly, in vivo the lowest concentration of Sutherlandia diet had the greatest effect on inhibition of poorly differentiated adenocarcinoma in the TRAMP mice. Conclusions: Sutherlandia's inhibition of prostate cancer growth may be via inhibition of hedgehog signaling. Future work to identify in Sutherlandia the active compound having this effect, and the ideal concentration for use in vivo may lead to a means whereby dietary intervention for prostate cancer prevention and/or treatment is possible. 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 1998. doi:1538-7445.AM2012-1998
Abstract 644: A novel Gemini vitamin D analogue represses the expression of a stem cell marker CD44 in breast cancer
Authors: Jae Young So, Hong Jin Lee, Amanda K. Smolarek, Shiby Paul, Hubert Maehr, Milan Uskokovic, Li Cai, Fang Liu, Nanjoo Suh
Journal: Cancer Research (2010)

Abstract Breast cancer stem cells are defined as cancer cells with self-renewal capacity. Cancer stem cells are resistant to current chemotherapy and radiation, making it difficult to investigate the mechanisms of resistance and the therapeutic targets of the tumor initiating cell population. Recently, CD44 has been recognized as a useful cell-surface marker for detecting breast cancer stem cells, and the CD44+/CD24- phenotype selects a population with stem cell properties similar to basal-like cancer cells. CD44 is a multi-functional transmembrane protein involved in cell proliferation, angiogenesis, invasion and metastasis. The CD44 positive subpopulation of breast cancer cells are enriched in residual breast cancer cell populations after conventional therapies, suggesting that CD44 positive cells may be responsible for the recurrence of cancer and therefore it may be an important therapeutic target. We have previously shown that novel Gemini vitamin D analogs inhibit the proliferation of breast cancer epithelial cells and suppress tumorigenesis in different animal models of breast cancer. Since therapies targeting CD44 by vitamin D have not been investigated, we examined whether a novel Gemini vitamin D analog regulates CD44 expression in cultured human breast cancer cells or in mammary tumors. In basal-like MCF10DCIS.com human breast cancer cells, the Gemini vitamin D analog BXL0124 significantly inhibited the expression of CD44 protein and reduced the transcriptional activity of the CD44 promoter in vitro. To evaluate the inhibitory effects of Gemini vitamin D on CD44 expression in vivo, MCF10DCIS.com cells were xenografted into immunodeficient mice. When administered intraperitoneally (0.1 microgram/kg body weight) or orally (0.3 microgram/kg body weight) once a day for 6 weeks, Gemini vitamin D BXL0124 inhibited tumor growth and markedly decreased the expression of CD44 in the xenograft tumors. To determine whether the repression of CD44 is dependent on the vitamin D receptor (VDR), siRNA VDR was employed. The repression of CD44 expression by BXL0124 was significantly blocked by siRNA VDR in MCF10DCIS.com cells, indicating that the regulation of CD44 expression by BXL0124 is a VDR-dependent event. Taken together, the novel Gemini vitamin D analog inhibits CD44 expression in MCF10DCIS.com cells in vitro and in xenograft tumors, suggesting an inhibitory role of Gemini vitamin D analogs on cancer stem 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 644.
AB0504 Vascular differences associated to genetic polymorphisms of endothelial nitric oxide synthase in mexican patients with systemic sclerosis.
Authors: M. P. D. P. Cruz-Dominguez, O. Vera-Lastra, M. A. Martinez-Godinez, A. Miliar-Garcia, D. H. Montes-Cortes, L. J. Jara, A. Reyes-Salazar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vascular dysfunction usually is observed before clinically detectable fibrosis of systemic sclerosis (SSc). The eNOS catalyses the synthesis of nitric oxide (NO), which maintains basal vascular tone and endothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing vascular disease. Genetic polymorphism may participatein these alterations. <h3>Objectives</h3> To investigate vascular differences associated to polymorphisms T-786C and G894T of the <i>eNOS</i> gene on differential expression of eNOS/iNOS in the skin and vascular Duplex Sonography parameters of SSc patients. <h3>Methods</h3> We included 139 consecutive SSc patients. The genotyping of T-786C and G894T polymorphisms of <i>eNOS</i> gene was performed by Polymerase Chain Reaction Real-Time Assay. The control group included 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc). <h3>Results</h3> In lcSSc: T-786C prevalence was TT65.5%, TC30.2% and CC4.3% (OR 1.8, IC 0.4–7.9 associated to SSc); and the G894T prevalence was GT74.3%, GT20.3% and TT5.4% (OR 1.94, IC 0.54–7.04 associated to SSc). In dcSSc: the T-786C prevalence was TT76.6%, TC20%, and CC3.3%, and G894T polymorphism was GT 82%, GT 18% and TT 0% withoutassociation with SSc. In control group: the prevalence of T-786C polymorphism was TT68.45%, TC29.4%, and CC2.22%; for G894T polymorphismwas GG74.1%, GT23.02%, TT2.87%. The mean relative expression of eNOS was 10.17+/-15.5 and iNOS of 7.6+/-13.05 in lcSSc. For dcSSc the mean relative expression of eNOS was 1.74+/-1.16 and iNOS of 2.1+/-2.5.1.08+/-0.3 and 1.36+/-0.7 in skin of volunteers of control+group. Left brachial intima-media thickness was statistically significantly greater in allelic variants of eNOS in SSc (p=0.025). <h3>Conclusions</h3> In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. Genetic polymorphisms of eNOS is associated with anormal intima-media thicknes in SSc patients. <h3>Disclosure of Interest</h3> None Declared
AB0702 Patients with antinuclear antibody-positive juvenile idiopathic arthritis consist of a homogeneous entity
Authors: X. Ma, F.-Q. Wu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> According to the International League of Associations for Rheumatology ILAR diagnostic criteria, some classifications of the official juvenile idiopathic arthritis JIA seem to represent distinct disease entities (systemic, polyarticular rheumatoid factor positive, oligoarthritis ), however, others seem to possess heterogeneous conditions (polyarticular rheumatoid negative, psoriatic). <h3>Objectives</h3> the purpose of this study is to discuss whether antinuclear antibody(ANA)-positive patients suffering from illness in the ILAR categories of oligoarthritis and rheumatoid factor-negative polyarthritis with homogeneous characteristics and to compare these characteristics with those of ANA-negative patients with the same categories of disease. <h3>Methods</h3> 120 patients, enrolled in Capital Pediatric Institute Rheumatology and Immunology Department from 2008 to 2011, accord with the ILAR criteria of oligoarthritis or polyarthritis. Of the 120 patients,49 were ANA positive (31 had oligoarthritis, 18 had RF-negative polyarthritis), and 71 were ANA negative (48 had oligoarthritis, 23 had RF- negative polyarthritis).ANA positivity was defined as more than twice positive results at a titer of ≧1:100. All of the clinical features were recorded retrospectively. <h3>Results</h3> ANA-positive patients of the two categories were semblable with respect to asymmetric arthritis and female-to-male ratio. Compared with ANA-positive patients with polyarthritis, ANA-negative patients with polyarthritis were a higher frequency of symmetric arthritis at disease presentation and six months after disease presentation, a more cumulative number of joints involved at nine or twelve months after diseasepresentation, and a distinctive type of joints, such as wrist, metacarpophalangeal and hip joints. Multiple logistic regression analysis were performed and the close correction between ANA positivity and asymmetric arthritis, female predominance and wrist involvement were corroborated. <h3>Conclusions</h3> JIA patients, who share the similar features including ANA positivity, female predominance and asymmetric arthritis, were divided into different subgroups by present ILAR criteria. The value of ANA positivity as a novel parameter of the present ILAR standard of classification deserves reference. <h3>References</h3> none <h3>Acknowledgements</h3> We thank LIU Zhe-weifor his help and guidance. The findings and conclusions in this report are those of the authors. <h3>Disclosure of Interest</h3> None Declared
472 HEPATOCELLULAR MxA PROTEIN EXPRESSION IS A POWERFUL PREDICTOR OF SUSTAINED VIROLOGICAL RESPONSE IN CHRONIC HEPATITIS C GENOTYPE 1 INFECTION USING A MULTIVARIATE LOGISTIC REGRESSION MODEL
Authors: A. Messineo, S. Duffy, Y. Huang, M. Platten, B. De Boer, G. Jeffrey, G. Mac Quillan
Journal: Journal of Hepatology (2013)
Abstract LB-286: 3p24 tumor suppressor gene RBMS3 in NPC
Authors: Juan Chen
Journal: Cancer Research (2012)

Abstract Deletion within the 3p chromosomal region are one of the most frequent genetic alterations in many solid tumors, including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3, located at the frequently deleted region 3p24-p23, has been identified in our previous study. Here, we reported that down-regulation of RBMS3 was detected in 3/3 (100%) NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional analysis demonstrated that RBMS3 was able to suppress tumorigenicity of NPC cells both in vitro and in vivo, including inhibiting the cell growth rate, colony formation in vitro and tumor formation in nude mice. Additionally, the tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by the up-regulation of p53, and p21, the down-regulation of Smad4, cyclin D1, cyclin E/CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of β-catenin and inactivation of its downstream targets, including c-Myc, MMP7, MMP9, and MMP2. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC. 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-286. doi:1538-7445.AM2012-LB-286
Myocardial Ischemia Caused by Distal Coronary-Artery Constriction in Stable Angina Pectoris
Authors: Giuseppe Pupita, Attilio Maseri, Juan Carlos Kaski, Alfredo R. Galassi, Stavros Gavrielides, Graham Davies, Filippo Crea
Journal: New England Journal of Medicine (1990)

In patients with stable coronary artery disease, the ischemic threshold for the production of effort-related angina is often quite variable. Although this feature is commonly attributed to changes in the caliber of coronary arteries at the site of stenosis, it could also be caused by the constriction of distal vessels, collateral vessels, or both.
Abnormalities of the p16INK4a gene in childhood B-precursor acute lymphoblastic leukemia without nonrandom translocations: analysis of seven matched pairs of primary leukemia and corresponding cell line
Authors: M Nakamura, K Sugita, T Inukai, K Goi, N Miyamoto, K Kagami, T Okazaki-Koyama, T Mori, M Saito, S Nakazawa
Journal: Leukemia (2001)
How and Why the National Cancer Institute Issued the Breast Cancer Clinical Alert
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article How and Why the National Cancer Institute Issued the Breast Cancer Clinical Alert Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 15, 5 October 1988, Pages 1186–1187, https://doi.org/10.1093/jnci/80.15.1186 Published: 05 October 1988
Effect of Gallium Nitrate Therapy on Ga-67 Scintigraphic Detection of Lymphoma:
Authors: GUR AKANSEL, YU LIU, CHRISTOPHER R. CHITAMBAR, MEHMET T. KITAPCI, SERTAC AKANSEL, ARTHUR Z. KRASNOW, ALI T. ISITMAN, B. DAVID COLLIER
Journal: Clinical Nuclear Medicine (1997)

Ga-67 and abdominal CT scans of a 72-year-old woman who had malignant lymphoma before, during, and after gallium nitrate/hydroxyurea combination therapy are presented. Disappearance of Ga-67 uptake by the tumor during this treatment despite continuing CT evidence of disease and reappearance of Ga-67 scan abnormalities after cessation of therapy suggests that caution should be exercised when interpreting results of Ga-67 scintigraphy for the detection of tumor viability during gallium nitrate/hydroxyurea therapy.
Abstract P4-02-15: Overlapping Therapy with High-Dose Tamoxifen and CYP2D6 Inhibitors Modifies Medication Adherence in Breast Cancer Patients
Authors: NJ Markward, J Tinnirello, M Khalid, FW Frueh, S Milayna, RE Aubert, RS. Epstein
Journal: Cancer Research (2010)

Abstract Background: Tamoxifen is a selective estrogen receptor modulator (SERM) commonly used to treat and prevent estrogen-receptor-positive (ERP) breast cancer. However, despite its established efficacy, recent studies indicate that 1 in 2 patients will discontinue use of the drug prior to completing the recommended five-year treatment cycle. The alleviation of unpleasant side effects through personalized targeting of tamoxifen dose and, as appropriate, concomitant administration of a CYP2D6 inhibitor could increase adherence and increase the likelihood that patients will receive the amount of the drug needed to protect them against disease onset and/or recurrence. Materials and Methods: A retrospective cohort study was implemented to assess whether overlapping therapy with highdose tamoxifen and CYP2D6 inhibitors influence medication adherence during the first 540 days of therapy. Subjects (N = 17,242) were identified in an integrated medical and pharmacy claims database and selected for inclusion in the study if they 1) filled a new tamoxifen prescription between 7/1/2008 and 6/30/2009 and 2) were continuously eligible to receive pharmacy benefits during the 6 months preceding and 12 months after initiation of therapy. Eligible participants were then cross-classified according to tamoxifen dose (NORMAL, HIGH) and CYP2D6 inhibitor status (NO, YES), and a Cox regression model was fitted to the data to obtain covariate-adjusted hazard ratios (HR) and 95% confidence intervals for each treatment combination relative to the HIGH/NO group. Results: The lowest and highest hazard ratios were observed in the NORMAL/YES [HR = 0.924 (0.88, 0.97)] and HIGH/NO [HR = 2.33 (2.07, 2.62)] categories. Moreover, the risk of discontinuation was significantly reduced when high-dose tamoxifen was administered in concert with a CYP2D6 inhibitor [HR = 1.31 (0.953, 1.802)]. Discussion: These study suggests that joint treatment with high-dose tamoxifen and a CYP2D6 inhibitor may improve tamoxifen adherence in breast cancer patients. The findings also highlight the need for 1) education and research regarding tamoxifen dosing and 2) careful consideration for when–and under what circumstances–concomitant medications should be prescribed to enhance patient tolerance of tamoxifen-related negative symptoms. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-15.