tbuckley/cabot-search huggingface dataset:
Abstract 1782: Regulation of ATM-dependent DNA damage signaling in human breast cancer cells by the RhoGEF Net1A .
Authors: Wonkyung Oh, Jeffrey A. Frost
Journal: Cancer Research (2013)

Abstract The Neuroepithelioma transforming gene 1 (Net1) is a RhoGEF that is frequently overexpressed in human cancer, including breast cancer. We have previously reported that DNA damage activates Net1 to control p38 MAPK signaling and protect cells from ionizing radiation (IR) induced apoptosis. However, others have shown that Net1 activation contributes to cell death by activating a RhoB-Bim signaling pathway. Thus, the role of Net1 in controlling IR responses and cell survival is controversial. Here we show that the Net1A isoform is uniquely important for DNA double-strand break (DSB)-induced signaling and DNA repair. SiRNA-mediated knockdown of Net1A in human breast cancer cells reduced IR-stimulated ATM activation and signaling to its substrates Chk2 and H2AX. In addition, suppression of Net1A expression adversely affected cell survival after IR. We also observed that Net1A overexpression significantly reduced γH2AX foci formation after IR, which required the unique N-terminal region of Net1A. Importantly, this effect did not require Rho GTPase activation by Net1A, and was not recapitulated by overexpression of RhoA or RhoB. Using comet assays, we found that Net1A depletion substantially slowed DNA DSB repair in response to IR. Intriguingly, knockdown of Net1A promoted non-homologous end joining (NHEJ) in the absence of DNA damage, and Net1A was found to co-immunoprecipitate with the DNA-PK complex in an IR-regulated manner. Taken together, these data suggest a model in which Net1A functions as a non-catalytic binding protein to control DNA damage response signaling and DNA repair to affect cell survival after IR. Citation Format: Wonkyung Oh, Jeffrey A. Frost. Regulation of ATM-dependent DNA damage signaling in human breast cancer cells by the RhoGEF Net1A . [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 1782. doi:10.1158/1538-7445.AM2013-1782
AI-26 * OVERCOMING RESISTANCE TO VEGF-BLOCKADE BY TARGETING THE ANGIOPOIETIN/TIE2 AXIS
Authors: A. Scholz, S. Cremer, P. Harter, M. Mittelbronn, P. van Slyke, D. Dumont, K. H. Plate
Journal: Neuro-Oncology (2014)

Angiogenesis inhibitors have evolved in the past decade as one of the most promising biology based therapeutic strategies. Pre-clinical studies (published in 1993 and 1994) provided proof of principle that blocking of VEGF dramatically inhibits tumor growth. These observations led to the successful development of inhibitors for VEGF and VEGF receptors by various pharmaceutical companies. Bevacizumab, a monoclonal antibody neutralizing VEGF, was the first-in-class drug to achieve FDA approval for the treatment of colorectal carcinoma in 2004 and later on in other cancer types, including glioblastoma. Anti-VEGF therapy led to an increase in progression free survival in recurrent and primary GBM, but its definite role in first-line-treatment is less clear. Importantly, several preclinical studies suggested that resistance to anti-angiogenic therapy might evolve in the course of the treatment due to an infiltration of specially polarized myeloid cells. In order to define new therapeutic options for anti-angiogenic therapy we investigated the potential role of Tie2/Angiopoietin (Ang) signaling pathway in human and murine glioblastomas. We here show by means of 1) transgenic mice overexpressing Angiopoietin-1 (GFAPtet/Ang-1), 2) transgenic mice overexpressing Angiopoietin-2 (Tie-1tet/Ang-2), 3) application of synthetic activators of the Tie2 receptor tyrosine kinase, 4) application of peptibodies targeting Ang-1 and Ang-2 and 5) application of monoclonal antibodies blocking Ang-2, that targeting of the Tie2/Angiopoietin signaling pathway leads to vascular normalization, diminished influx of myeloid cells and prolonged overall survival in mice pretreated with VEGF-blockers. These findings suggest that targeting of the Tie2/Angiopoietin pathway, even alone or in combination with VEGF inhibition, might be a potential therapeutic option for glioblastoma therapy.
Abstract 359: Neuropeptides promote castration-resistant prostate cancer through intracrine androgen biosynthesis
Authors: Joy C. Yang, Hsing-Jien Kung, Allen C. Gao, Christopher P. Evans
Journal: Cancer Research (2011)

Abstract Introduction and Objectives: Neuroendocrine differentiation is associated with castration resistant prostate cancer (CRPC) with detectable increased serum levels of chromogranin A in patients. Neuropeptides secreted from the neuroendocrine cells are believed to activate androgen receptor (AR) in low or no androgen environments. We hypothesize that neuropeptides sustain CRPC by promoting intracrine androgen synthesis. Methods: We engineered LNCaP cells overexpressing gastrin-releasing peptide (GRP) and examined the level of androgen biosynthetic enzymes by RT-PCR and Western blots. Inhibition of androgen-free growth of LNCaP-GRP cells was performed with siRNA to AKR1C3 or CYP17A1 with or without Src inhibitor saracatinib. PSA and total testosterone levels were assessed in LNCaP-GRP cells, serum from tumor-bearing animals and xenografts. Results: The androgen biosynthetic enzymes were up-regulated in LNCaP-GRP cells, with AKR1C3, CYP17A1 and HSD17B2 displaying over 40 fold increase compared to the control line by real-time RT-PCR analysis. Transfection of siRNA against AKR1C3 and CYP17A1 inhibited LNCaP-GRP cell growth in androgen-free medium. Specific Src family kinase inhibitor saracatinib inhibits androgen-independent LNCaP-GRP cell growth in vitro and tumor metastasis in vivo. Saracatinib also reduced the expression of AKR1C3, AKR1C1/2 and HSD3B1/2 in GRP cells at both RNA and protein levels. When combined with siRNA for AKR1C3 and CYP17A1, saracatinib further inhibited androgen-independent LNCaP-GRP cell growth. Testosterone was detectable by EIA assay in LNCaP-GRP cell lysates (109.1 and 44.5 pg/mg protein vs. 18.3 in control), serum from castrated mice bearing GRP tumors (2235.5 pg/ml serum) and xenograft tissue (59.2 pg/mg tumor). These enhanced T levels were greatly reduced when treated with saracatinib, to 594 pg/ml serum and 12 pg/mg tumor, respectively. Conclusions: Secretion of neuropeptides promotes CRPC through up-regulation of intracrine androgen biosynthesis. Saracatinib not only targets neuropeptide-mediated AR activation but also blocks steroidogenesis in CRPC. 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 359. doi:10.1158/1538-7445.AM2011-359
‘Patria, Honor y Fuerza’: A Study of a Right-Wing Youth Movement in Mexico during the 1930s–1960s
Authors: CLAIRE BREWSTER, KEITH BREWSTER
Journal: Behavioral and Brain Sciences (2014)

Abstract This article focuses on the intricate and developing nature of official politics and grassroots activism in post-revolutionary Mexico. It does so by tracing the trajectory of the Pentathlón Deportivo Militar Universitario, a right-wing youth movement that emerged in Mexico in 1938. By locating the group within both the international and domestic emergence of youth movements in the early twentieth century, the article shows how the study of Pentathlón's formation, objectives and later evolution can significantly enrich our understanding of an important phase in Mexico's post-revolutionary history. Within the context of right wing oppositional politics, analysis of the movement provides a fascinating insight into both the emerging Mexican state's ability to appropriate the radical impulses of the younger generation and the Pentathlón's willingness to accommodate such strategies in order to ensure its own survival.
AB1234 Clinical characteristics of IgG4-related orbital pseudo-tumor
Authors: T. Origuchi, S.-Y. Kawashiri, K. Ichinose, M. Tamai, K. Arima, S. Yamasaki, H. Nakamura, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a new emerging disease entity of unknown etiology with multiorgan involvement. IgG4-RD includes a wide variety of diseases, including Mikulicz's disease (MD), autoimmune pancreatitis (AIP), hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudo-tumor. It was thought that almost orbital pseudo-tumors were idiopathic except malignant lymphoma. However, recently, IgG4-RD was suspected to be an origin of orbital pseudo-tumor. <h3>Objectives</h3> We clarified the characteristics of IgG4-related disease manifested by orbital pseudo-tumor. <h3>Methods</h3> We examined three cases of IgG4-related orbital pseudo-tumor. We summarized the radiographic and pathological characteristics of IgG4-related orbital pseudo-tumor. <h3>Results</h3> Patients were 64-75 year-old men. They noticed a mass lesion in an upper eyelid and received an operation for the removal of the mass. A histopathological examination revealed the accumulation of IgG4 positive plasma cells (IgG4/IgG ratio:40.0-51.1%). The serum level of IgG4 was 178-666mg/dl. MRI revealed low T1 intensity and low T2 intensity in three cases. In one case, Gallium scintigraphy showed hot spots in right parotid gland, bilateral submandibular glands, neck and hilar lymph nodes. And in another case, it showed an accumulation in bilateral hilar lymph nodes, right side of thoracic vertebrae and ileocecum. <h3>Conclusions</h3> We found three IgG4-related diseases in the cases who had orbital mass lesions. We also suggested that a histopathological examination and serum IgG4 concentration were important for the diagnosis of IgG4-related disease in orbital mass lesions. <h3>References</h3> Masaki Y, Dong L, Kurose N, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009 68(8):1310-5. <h3>Disclosure of Interest</h3> None Declared
Impact of Various Types of Genetic Damage and Risk Assessment
Authors: James F. Crow
Journal: Environmental Health Perspectives (1973)

I should like to review very briefly the various kinds of genetic damage that might be expected to occur from chemical mutagens, the time delay before such effects might be manifest, and something of the kind of impact that these might be expected to have on human well-being. I hardly need to add that this is an area where we know very little; we know enough to be apprehensive, but not enough to be at all certain. My remarks will draw heavily from two recent reports on radiation effects, the National Academy of Sciences Report (1) and the United Nations Report (2). In the area of radiation protection there are standards which are agreed to internationally and which form the basis of radiation protection policy. I suggest that in the area of chemical mutagenesis we can obtain considerable guidance from the older field of radiation mutagenesis. I shall have a specific suggestion later as to how radiation standards can be used as a starting point in setting limits for chemical mutagens.
Abstract 4427: Role of cytochrome P450 (CYP)1A2 in the sustained induction of CYP1A1 by the carcinogen, 3-methylcholanthrene (MC) in mouse heptoma cells (hepa-1)
Authors: Bhagavatula Moorthy, Sudha R. Kondraganti, Lihua Wang, Weiwu Jiang, Chun Chu
Journal: Cancer Research (2012)

Abstract Humans are constantly exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (PAHs) through cigarette smoke, diesel exhausts, charcoal-broiled meats, etc. Cytochrome P4501A (CYP1A) enzymes play important roles in the activation of PAHs such as 3-methylcholanthrene (MC) to carcinogenic DNA-binding metabolites. We reported earlier that MC causes persistent induction of hepatic and pulmonary CYP1A1 in mice for several weeks after MC ithdrawal, and that the phenomenon of sustained hepatic CYP1A1 induction is lost in Cyp1a2-null mice. In this study, we tested the hypothesis that MC elicits induction of persistent CYP1A1 nduction in hepa-1 cells, and that CYP1A2 contributes mechanistically to this henomenon. Hepa-1 cells were treated ith the MC (2.5 µM), or dimethylsulfoxide (DMSO) as control, and at selected ime points, CYP1A1 promoter activity, CYP1A1 enzyme activities, contents, and CYP1A1 mRNA levels were studied. We fund that MC markedly and persistently induced CYP1A1 promoter activity, transcription, apoprotein expression, and the CYP1A1 associated ethoxyresorufin O-deethylase (EROD) activities for up to 5 days. Transfection of CYP1A2 siRNA resulted in knockdown of CYP1A2 mRNA by 70%, but a statistically significant increase of basal CYP1A1 mRNA by 35-40%. The induction of CYP1A1 promoter ctivity, CYP1A1 mRNA, CYP1A1 protein, and EROD activity by MC were not affected by CYP1A2 siRNA at the 24 h time point, but was significantly ttenuated by Cyp1a2 siRNA on day 5. These results suggest that CYP1A2, possibly via a metabolite, contributes to the sustained induction of CYP1A1 by MC in hepa-I cells. Further investigations into the mechanisms of persistent induction of CYP1A1 by MC could lead to novel preventative/therapeutic strategies against PAH-mediated carcinogenesis in humans. (Supported in part by 2R01 ES009132.) 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 4427. doi:1538-7445.AM2012-4427
Life-Threatening Hemorrhage of an Unanticipated Superficial Circumflex Iliac Artery Origin Imaged With Tc-99m–Labeled Erythrocytes
Authors: S Passarell, L E Holder, G Hastings
Journal: Clinical Nuclear Medicine (2000)

The authors report, for the first time, the nuclear medicine diagnosis of extraperitoneal bleeding that originated from the superficial circumflex iliac artery and review the critical role of dynamic nuclear imaging techniques in the localization of sites of nonenteric hemorrhage. Dynamic imaging techniques using Tc-99m– labeled erythrocytes played a critical role in the localization of an extraperitoneal bleeding site near the entrance site of a Jackson–Pratt drain. Localization of the site remained undiagnosed before nuclear imaging despite two exploratory laparotomies and diagnostic angiography.
Aspirin, Heparin, or Both to Treat Acute Unstable Angina
Authors: Pierre Théroux, Hélène Ouimet, John McCans, Jean-Gilles Latour, Patrick Joly, Gilles Lévy, Edouard Pelletier, Martin Juneau, Jérôme Stasiak, Pierre deGuise, Guy B. Pelletier, David Rinzler, David D. Waters
Journal: New England Journal of Medicine (1988)

We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [±SD] of 7.9±8.0 hours after the last episode of pain), and the study was ended after 6±3 days, when definitive therapy had been selected. Major end points — refractory angina, myocardial infarction, and death — occurred in 23,12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P<0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina. (N Engl J Med 1988; 319:1105–11.)
Laterally Shifted Urinary Bladder Mimicking a Supernumerary Kidney
Authors: SLEIMAN Y. NADDAF, MAHMOUD A. ALFEELI, BERT DAVID COLLIER
Journal: Clinical Nuclear Medicine (2003)

NADDAF, SLEIMAN Y. M.D.; ALFEELI, MAHMOUD A. M.D.; DAVID COLLIER, BERT M.D. Author Information
WORSENING RENAL FUNCTION DURING AGGRESSIVE HEART FAILURE MANAGEMENT IS NOT ASSOCIATED WITH POOR OUTCOMES: RESULTS FROM THE PRO-BNP OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY
Authors: Nasrien E. Ibrahim, Hanna K. Gaggin, Dustin J. Rabideau, James Januzzi
Journal: Journal of the American College of Cardiology (2016)
In-111 Pentatreotide Uptake in a Chondrosarcoma
Authors: KIRKMAN G. BAXTER, HOWARD G. ROSENTHAL, MARK L. REDICK, DAVID PRESTON
Journal: Clinical Nuclear Medicine (1996)

A 25-year-old man presented with a large left buttock mass, present for approximately 7 years. The mass was slowly enlarging during the past 2 years. Radiographic evaluation included plain films and CT of the pelvis and bone scintigraphy. A pentreotide study also was performed during the diagnostic work-up and showed diffuse uptake throughout the tumor. Pathologic diagnosis confirmed the radiologic findings of a chondrosarcoma. In-111 pentreotide (Octreotide®), a somatostatin analogue, accumulates in tumors with somatostatin receptors. The authors' study shows uptake in a soft-tissue sarcoma, previously not reported as a tumor type that accumulates pentreotide.
The Role of microRNA Genes in Breast Cancer Progression and Metastasis.
Authors: C. Johnstone, E. Lucas, L. Kusdra, A. Goga, R. Anderson
Journal: Cancer Research (2009)

Abstract MicroRNAs influence tumor progression and metastasis via action as metastasis promoting genes (for example mir-373 and mir-520) or metastasis suppressor genes (for example mir-335). To identify additional microRNAs capable of driving breast cancer metastasis in vivo, we employed a functional genomics screen using the '4T1' syngeneic (Balb/c) mouse model of breast cancer progression. Approximately 400 microRNA sequences were subcloned into the pMSCV_puro retroviral expression vector and the resultant microRNA expression library transduced into fluorescent non-metastatic 67NR-pMSCV_mCherry and mildy-metastatic 66cl4-pMSCV_mCherry cells and selected with puromycin. The transduced cell lines were then implanted into the mammary fat pads of 20 syngeneic Balb/c mice per cell line. Following establishment of primary tumors, the primary tumors and secondary organs (lung, liver, spine, femurs), including any overt metastatic deposits, were dissected under a fluorescent stereomicroscope and the microRNA inserts amplified from the integrated retroviral genome by PCR.In an alternative approach, we have studied two populations of MDA-MB-231 human breast cancer cells that exhibit different behavior in vitro and in vivo to elucidate processes involved in cellular invasion and metastasis. A late-passage MDA-MB-231 (231variant) population formed invasive clusters when embedded in Matrigel, whereas early-passage (P3) MDA-MB-231 (231) cells did not. Moreover, 231v cells were more motile than 231 cells and showed enhanced tumorigenicity when grown as subcutaneous xenografts in nude mice, whereas proliferation and apoptotic response were indistinguishable between the two lines in vitro. Molecular characterization of the two cell populations cultured in 3D by array-based gene expression profiling revealed elevated expression of NF kappa B target genes in 231v cells (IL1A, IL1B, IL6, PTX3, NR4A2, HMOX1, FLIP). MicroRNA array analysis of 3D cultures also revealed marked induction (approximately 8-fold) of the related NF kappa B target microRNAs, mir-146a and mir-146b (Figure 1). Further evaluation of a panel of human breast cancer cell lines revealed that mir-146a and mir-146b were dramatically elevated in metastatic human breast cancer cell lines that display both epithelial-to-mesenchymal transition and high NF kappa B activity (MDA-MB-231, Hs578T, MDA-MB-436), compared to non-metastatic lines. Experiments to elucidate the function of mir-146a and mir-146b during breast cancer progression are underway. Figure 1: TaqMan qPCR analysis of mir-146a and mir-146b expression in 231 and 231v cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6142.
Abstract 5619: Exploration of pleiotropic effects of cancer GWAS hits with risk of endometrial cancer in the PAGE study
Authors: Ulrike Peters, Megan Fesinmeyer, Cara Carty, Jonathan Kocarnik, Yi Lin, Jeffrey Haessler, Charles Kooperberg
Journal: Cancer Research (2011)

Abstract Introduction: Endometrial cancer is the most common gynecological cancer in developed countries. While so far no genome-wide association study (GWAS) has been published for endometrial cancer this approach has been very successful in identifying susceptibility loci for various cancer sites. Interestingly, these GWAS have discovered susceptibility loci that are associated with multiple cancer sites, such as in the 8q24 or TERT-CLPTM1L locus. To comprehensively explore such pleiotropic effects for endometrial cancer we evaluated whether GWAS hits for different cancer sites are associated with risk of endometrial cancer. Methods: We included 965 endometrial cancer cases and 5759 controls aged 50-79 years from the Women's Health Initiative, which were genotyped as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. We selected 175 single nucleotide polymorphisms (SNPs) previously shown to be associated with different cancer sites mostly in GWAS. We coded SNPs using additive genetic models and used logistic regression to estimate per allele odds ratios (OR) and 95% confidence intervals (CI). Race/ethnicity-specific models were adjusted for age and post-menopausal hormone use. Results: Among whites the two most independent significant SNPs were rs7501939/17q12 [odds ratio (OR)=0.82; 95% confidential interval (CI)=0.74-0.92; p-value=3.4e-4], and rs4324715/5q31 (OR=0.85; 95%CI=0.76-0.94; p-value=1.5e-3). Interestingly, these two variants have been related to cancers of the male reproductive system (prostate and testicular cancer, respectively) in prior GWAS. When adjusting for multiple comparisons (p=2.86e-4) only one variant (rs7501939) remained marginally significant. The number of other ancestral groups, such as African American or Asian (n=72) was too small to allow separate analysis. Conclusion: This first analysis suggests that susceptibility loci of the male reproductive system may be associated with endometrial cancer. The next step in this analysis will be to incorporate data from the other PAGE studies to improve the power, explore effects across different ethnicities and to expand our analysis to evaluate gene-environment interactions, particularly looking at hormone related factors. 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 5619. doi:10.1158/1538-7445.AM2011-5619