tbuckley/cabot-search huggingface dataset:
Abstract 703: Suppression of neurotensin receptor type 1 expression and function by apigenin in human colorectal cancers involves protein kinase CK2/JNK pathway
Authors: Xiaofu Wang, Pat Gulhati, Piotr G. Rychahou, Scott R. Silva, B. M. Evers
Journal: Cancer Research (2010)

Abstract Apigenin, a nonmutagenic chemopreventive agent found naturally in fruits and green vegetables, is an inhibitor of protein kinase CK2 (formerly casein kinase II), which is frequently upregulated in human cancers. Neurotensin (NT), a gut peptide, stimulates growth of colorectal cancers (CRCs) through its high affinity receptor (NTR1). In this study, we found that treatment with apigenin suppressed NTR1 expression in CRC cells HCT116, SW480 and SW620. Additionally, treatment with emodin, another natural inhibitor of CK2, and TBB (4,5,6,7-tetrabromo-1H-benzotriazole), a selective chemical inhibitor of CK2, suppressed NTR1 expression in these CRC cells, indicating that CK2 plays a role in NTR1 regulation. Moreover, apigenin significantly decreased phosphorylation of JNK1/2, whereas TBB decreased phosphorylation of JNK1 and emodin decreased phosphorylation of JNK2 in HCT116 cells; all three compounds decreased phosphorylation of JNK1 in SW480 cells. Treatment with the selective JNK1/2 inhibitor, SP600125, suppressed NTR1 expression in all CRC cell lines examined. Furthermore, apigenin significantly inhibited CRC cell proliferation and prevented NT-stimulated expression of IL-8, c-myc and Mcl-1, all which contribute to CRC proliferation or metastasis. We conclude that apigenin suppresses endogenous NTR1 expression and function in multiple CRC cell lines; this effect may involve CK2/JNK signaling. The downregulation of NTR1 in CRCs may represent an important mechanism for the anti-cancer effects of apigenin. 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 703.
O1.04 * ROLE OF AQUAPORIN4 IN HUMAN BRAIN METASTASES: STUDY OF 60 CASES
Authors: B. Pollo, S. Mazzetti, M. Patane, C. Calatozzolo, F. Cacciatore, A. Silvani, F. Di Meco, R. Nunziata
Journal: Neuro-Oncology (2014)

Aquaporin4 (AQP4) is the main water channel in the central nervous system and is localized in the astrocytic endfoot processes. AQP4 is involved in important physiological functions, such as water balance and also in neural signal transduction. When the blood-brain barrier become disrupted, as in the case of pathological conditions, such as in brain tumor, water moves from the vasculature into the extracellular space in an AQP4-independent manner, down a hydrostatic gradient to form a vasogenic edema. Moreover, in cancer AQPs have a role promoting tumor progression, invasion and metastasis. The AQP4 contribution to the brain metastasis has not been previously investigated. The aim of our study was to analyze AQP4 distribution in 60 human brain metastases of tumor from lung (n = 20), breast (n = 20), colon (n = 5), kidney (n = 8), melanoma (n = 2), thyroid (n = 1), ovary (n = 3) and prostate (n = 1), using immunohistochemistry and, in some cases western blotting. AQP4 expression on metastasis was related to clinical data of the patients. Our results revealed that: 1) normal brain near metastasis showed an increase of AQP4 expression, accompanied with gliosis; 2) at the metastasis-brain interface, AQP4 staining was increased in all kind of tumor analyzed; 3) AQP4 staining strictly surrounded each metastatic cell, also in some areas in tumor core near vessels, especially in lung and breast; 4) some metastasis from NSCLC showed membrane AQP4 immunostaining. These observations together suggest a beneficial role of AQP4 in the brain edema caused by the metastatic event, indicating that AQP4 expression may restore a normal perivascular rearrangement, also at the periphery of the tumors. Moreover, great AQP4 expression seems to correlate to higher differentiation and a better prognosis. Our findings support to consider AQP4 as a promising therapeutic target.
282 NUCLEAR TRANSLOCATION OF ß-CATENIN DURING MESENCHYMAL STEM CELLS DIFFERENTIATION INTO HEPATOCYTES IS ASSOCIATED WITH LIVER CANCER-RELATED PROTEINS
Authors: C. Herencia, J.M. Martinez-Moreno, C. Herrera, F. Corrales, I. Espejo, M. Barco, Y. Almaden, M. de la Mata, A. Rodriguez-Ariza, J.R. Munoz-Castaneda
Journal: Journal of Hepatology (2012)
Abnormal Hypothalamic–Pituitary–Adrenal Function in Anorexia Nervosa
Authors: Philip W. Gold, Harry Gwirtsman, Peter C. Avgerinos, Lynnette K. Nieman, William T. Gallucci, Walter Kaye, David Jimerson, Michael Ebert, Roger Rittmaster, D. Lynn Loriaux, George P. Chrousos
Journal: New England Journal of Medicine (1986)

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.
FRI0209 Intravitreal infliximab for sight-threatening acute uveitis attacks in behcet’s disease: A pilot study in 15 patients
Authors: N. Markomichelakis, E. Delicha, S. Masselos, P.P. Sfikakis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Intravenous administration of the anti-TNF monoclonal antibody infliximab results in rapid and effective suppression of posterior eye segment inflammation, thus avoiding development of permanent lesions in the retina and optic disc, in many patients with Behcet's disease (BD). Since infliximab may reactivate latent tuberculosis which is particularly prevalent in countries where BD is endemic, whereas history of cancer or congestive heart failure are contraindications for systemic anti-TNF treatment, an intravitreal injection with minimal systemic absorption could be preferable providing that therapeutic intraocular concentrations can be achieved. Along this line, recent experimental studies on intraocular administration of infliximab have been conducted. <h3>Objectives</h3> To assess the efficacy and safety of a single intravitreal injection of the infliximab for sight–threatening uveitis attacks in BD. <h3>Methods</h3> In this prospective, non-comparative, interventional study 15 patients with acute unilateral posterior uveitis were given intravitreal infliximab (1mg/0.05mL) at attack's onset. Oral medications at the day of ocular attack included combinations of azathioprine/cyclosporine-A/corticosteroids (n=1), azathioprine/corticosteroids (n=2), cyclosporine-A/azathiorpine (n=3), or monotherapy with azathioprine (n=4), cyclosporine-A (n=1), or no treatment (n=4). Best corrected visual acuity (BCVA), anterior chamber cells, vitreous cells and posterior eye segment inflammation were assessed at baseline, 1, 7, 14, and 30 post-treatment days. Other medications remained unchanged. <h3>Results</h3> Baseline BCVA (mean logarithm of the minimum angle of resolution of 0.74, range 0.15-1.7) improved significantly by day 7 and continued to improve through day 30 after infliximab (mean of 0.30, p&lt;0.0001). Profound decreases in anterior chamber cells (p&lt;0.0001), vitreous cells (p&lt;0.0001), and beneficial effects in retinal vasculitis (p=0.0001) and retinitis (p=0.001) were evident through day 30. Although cystoid macular edema persisted at follow-up end in 9 of 11 eyes affected, central macular thickness decreased significantly by day 7 and continued to decrease through day 30 (p&lt;0.0001). Total inflammation score decreased from 6.27 (baseline mean) to 4.13, 2.87 and 1.13 (days 7, 14 and 30, respectively), being 0 at follow-up end in 6/15 eyes. Background medications were not associated with response to infliximab. No ocular or extra-ocular side effects were noted. <h3>Conclusions</h3> These findings confirm that intraocularly produced and/or acting TNF is crucial in BD-associated uveitis and suggest that intravitreal infliximab should be considered when systemic administration is not feasible or contraindicated. Further studies may identify patients for whom intravitreal delivery of infliximab could be preferable to systemic treatment. <h3>Disclosure of Interest</h3> None Declared
P743Hypercholesterolemia leads to hyperactivation of mononuclear cells by increased intracellular signaling and as a result of enhanced chemokinesis
Authors: K Tjaden, C Adam, E Pardali, J Waltenberger
Journal: Cardiovascular Research (2014)

Purpose: Monocytes contribute to both vacular repair as well as atherogenesis. This contribution is dependent on monocyte function. Hypercholesterolemia (HC) is a cardiovascular risk factor affecting monocyte function and resulting in reduced chemotactic response towards chemokines such as VEGFA ("VEGF resistance") or MCP-1. The aim of the current project is to investigate the molecular mechanisms underlying HC-related monocyte dysfunction resulting in VEGF resistance.
Incidental 11C-Choline PET/CT Uptake Due to Esophageal Carcinoma in a Patient Studied for Prostate Cancer
Authors: Francesco Bertagna, Mattia Bertoli, Giorgio Treglia, Stefania Manenti, Marianna Salemme, Raffaele Giubbini
Journal: Clinical Nuclear Medicine (2014)

A 75-years-old patient with a history of prostate cancer, previously treated with radical prostatectomy, underwent C-choline PET/CT for restaging due to a rise in the prostate-specific antigen level. The study revealed a focal uptake of C-choline in the esophagus. A subsequent endoscopic examination showed the presence of an esophageal lesion, and after surgery, the histologic diagnosis was mildly differentiated squamous cell carcinoma. In our case, the incidental esophageal uptake revealed by C-choline PET/CT allowed the early diagnosis of an unsuspected esophageal carcinoma.
AT-53 * PHASE I/II STUDY OF DIANHYDROGALACTITOL IN PATIENTS WITH RECURRENT MALIGNANT GLIOBLASTOMA MULTIFORME (GBM)
Authors: K. Shih, M. Patel, N. Butowski, J. Bacha, D. Brown, W. Garner, A. Steino, R. Schwartz, S. Kanekal, L. Lopez, H. A. Burris
Journal: Neuro-Oncology (2014)

Median survival for patients with recurrent GBM is <6 months. Front-line systemic therapy is temozolomide but resistance due to O6-methylguanine-DNA-methyltransferase (MGMT) activity is implicated in poor outcomes. Dianhydrogalactitol (VAL-083) is a structurally unique bi-functional DNA alkylating agent that accumulates in brain tumor tissue. In in vitro studies, VAL-083 demonstrated activity in pediatric and adult GBM cell lines, as well as GBM cancer stem cells. Notably, VAL-083 overcomes resistance to MGMT in vitro. Previous clinical studies suggest that VAL-083 has anti-tumor activity against a range of tumors, including GBM. In light of extensive safety data from clinical trials and promising efficacy in CNS tumors, we initiated a new clinical study to establish the maximum tolerated dose (MTD) and identify a dose and dosing regimen for future efficacy trials in GBM. Early in the development of VAL-083, a cumulative IV dose of 125 mg/m2 delivered in a 35 day cycle in combination with radiation was shown superior to radiation alone in brain cancer (Eagan, et al. 1979). In the present study, the cumulative dose in a 33 day cycle ranges from 9 mg/m2 (cohort 1) to 240 mg/m2 (cohort 7). Six dose cohorts have completed the trial with no drug-related serious adverse events: MTD was not yet reached. Enrollment for cohort 7 (33 day cumulative dose: 240 mg/m2) has been initiated and higher doses may be explored; the results will determine the design of the safety and efficacy registration trial. METHODS: Open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed initial diagnosis of malignant GBM. The study utilizes a 3 + 3 dose-escalation design. Patients receive VAL-083 IV on days 1, 2, and 3 of a 21 day cycle. GBM patients previously been treated with surgery and/or radiation, if appropriate, must have failed both bevacizumab and temozolomide, unless contraindicated. ClinicalTrials.gov Identifier NCT01478178.
P2-01-10: Blockage of Autocrine TGF-b Signaling Reduces Tumorigenecity and Lung Metastasis in a Murine Breast Cancer Cell Line, NMuMG-ST.
Authors: Z Liu, NW Robert, L Wang, A Bandyopadhyay, L-Z Sun
Journal: Cancer Research (2011)

Abstract Transforming growth factor beta (TGF-b) is known to have a dualistic role in breast cancer cells, acting as a tumor suppressor or a tumor promoter. This dualistic property varies in different cells and at different progression stages. Studies show that autocrine TGF-b is necessary for the growth and survival of MDA-MB-231 cells, and was also known to enhance the survival of MCF-7 cells. However, the role of autocrine TGF-b in spontaneously transformed cells is still less understood. We have retrovirally transduced a dominant negative TGF-b Type II receptor (DN RII) into a spontaneously transformed murine mammary gland epithelial cell line NMuMG-ST (DN RII cells). The expression of DN RII reduces TGF-b sensitivity of NMuMG-ST cells in a gene transcription assay and a growth inhibition assay. Interestingly, the autocrine TGF-b supports the survival of NMuMG-ST cells, although the exogenous TGF-b inhibits the growth of NMuMG-ST cells. Moreover, more apoptosis were observed in the DN RII cells compared to the control cells in both in vivo and in vitro experiment. We found that AKT and ERK pathway mediates autocrine TGF-b's survival signal. Results of western immunoblot for several stem cell markers and mammosphere formation assay suggest that autocrine TGF-b signaling is essential for the maintenance of stem like cell subpopulation in NMuMG-ST cells. By using immunocytostaining, we found that the DN RII cells expressed more E-cadherin and less Vimentin when compared to the control NMuMG-ST cells, which indicate that blocking autocrine TGF-b signaling pathway could inhibit the process of EMT in NMuMG-ST cells. Notably, when the cells were inoculated orthotopically in nude mouse mammary glands, tumors formed by DN RII cells grew at a similar rate as those formed by control cells, but caused fewer lung metastases. Our finding identified that the autocrine TGF-b signaling is important for the survival and metastatic ability of NMuMG-ST, which could provide an important foundation for further investigation on the role of autocrine TGF-b signaling in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-10.
SAT0390 Differential FDG-PET/CT findings for spondylarthropathies, PMR, and RA
Authors: H. Yamashita, Y. Takahashi, H. Kaneko, K. Kubota, T. Kano, A. Mimori
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We assessed similarities and differences in fluorine-18 (<sup>18</sup>F)-labelled fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with seronegative spondyloarthropathy (SpA), polymyalgia rheumatica (PMR), and rheumatoid arthritis (RA). <h3>Methods</h3> This study included 51 patients with SpA (<i>n</i> =19), PMR (<i>n</i> =16), or RA (<i>n</i> =16) who were admitted to our hospital between 2006 and 2011. Disease activities in the ischial tuberosities, greater trochanters, spinous processes, vertebral bodies, and sacroiliac joints (SIJs) were evaluated for FDG accumulation using maximum standardised uptake values (SUV<sub>max</sub>) and FDG scores. <h3>Results</h3> SUV<sub>max</sub> for ischial tuberosities was significantly higher in patients with PMR than in those with SpA or RA. SUV<sub>max</sub> for greater trochanters and spinous processes were significantly higher in patients with PMR than in those with RA (<i>P</i>&lt;0.001). SUV<sub>max</sub> for SIJs was significantly higher in patients with SpA than in those with PMR or RA (<i>P</i>=0.01).No significant difference in vertebral scores was observed among groups (<i>P</i>=0.488). Similar results were obtained when each site was evaluated using FDG scores. X-ray findings were consistent with PET/CT findings in 3/15 (20%) patients with sacroiliitis, while magnetic resonance imaging findings were consistent with PET/CT findings in 4/7 (57.1%) patients. <h3>Conclusions</h3> PET/CT detection of inflammation in the ischial tuberosities, greater trochanters, and spinous processes discriminated between PMR and RA, but not between SpA and PMR. PET/CT findings for SIJs are useful for distinguishing SpA from RA and PMR and for the early diagnosis of sacroiliitis. <h3>Disclosure of Interest</h3> None Declared
Abstract 2652: Multiplex detection of stem cell pluripotency markers in reference cancer cell lines.
Authors: Frederick W. Wiese, Nikolai Stankiewicz, Ralf Reiners, Tim Warmke, Reeti Maheshwari
Journal: Cancer Research (2013)

Abstract Several proteins, including Oct-3/4, Sox2, KLF4 and Nanog, play a critical role in the maintenance of pluripotency in stem cells. Overexpression of one or a combination of these factors has been reported in solid tumors from a variety of tissues. The presence of pseudogenes and differentially expressed protein isoforms complicates the accurate detection of the physiologically relevant forms of these proteins in cancer stem cell research. Here, we report the development of MILLIPLEX® MAP multiplex assays for the simultaneous, specific and sensitive detection of the pluripotency markers Oct-3/4, Sox2, KLF4 and Nanog as well as several other stem cell relevant proteins in cellular lysates. Application of the assay to a panel of 25 human cancer cell lines from a variety of organs revealed Sox2 to be the most often expressed protein among these lines. Of the cell lines assayed, only one breast cancer cell line expressed detectable levels of all three transcription factors, suggesting a role for Oct3/4, Sox2 and Nanog in cancer stem cells of this particular cell line. These experiments demonstrate the utility of this pluripotency marker panel for the sensitive analysis of stem cells from a variety of lineages. The expression of the panel analytes was also examined in induced pluripotent stem cells (iPS) and a human embryonic stem cell (hES) line for reference. Taken together we show the successful development of a multiplex immunoassay that can be used to investigate the role of pluripotency marker proteins in stem cells or cancer cell immortalized or primary lines. Citation Format: Frederick W. Wiese, Nikolai Stankiewicz, Ralf Reiners, Tim Warmke, Reeti Maheshwari. Multiplex detection of stem cell pluripotency markers in reference cancer cell lines. [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 2652. doi:10.1158/1538-7445.AM2013-2652
Abstract 4292: RasGRP3 contributes to Ras signaling, growth, and migration of human lung cancer cell lines.
Authors: Jing Yang, Timothy Esch, Dazhi Yang, Peter Blumberg
Journal: Cancer Research (2013)

Abstract Elevated levels of Ras activity are a prominent feature in human lung cancer. In approximately 20% of lung cancer cases, Ras activation is achieved by mutation of the Ras proto-oncogene. Here, we explore the possible contribution of RasGRP3 to Ras signaling in lung cancer. RasGRP3 is a Ras guanyl nucleotide exchange factor which has been shown to be expressed in prostate tumor and melanoma cell lines, contributing to the level of Ras activation, cell proliferation, and tumor xenograft growth. Here, we report that RasGRP3 is expressed in multiple human lung cancer cell lines but not in normal human bronchial epithelial cells. Likewise, initial analysis reveals its expression in human lung tumors but not in normal lung tissue. Suppression of endogenous RasGRP3 expression in lung cancer cell lines showing reduced H-Ras-GTP and K-Ras-GTP formation as well as Akt phosphorylation downstream from epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA) stimulation. Additionally, suppression of RasGRP3 inhibited translocation of the NF-kB p50 and p65 subunits from the cytoplasm to the nuclear fraction and modulated several other transcriptional factors as well. Conversely, expression of exogenous RasGRP3 elevated H-Ras-GTP and K-Ras-GTP and activated AKT phosphorylation in the lung cancer H496 cell line, which itself only expresses RasGRP3 at low levels. These changes in signaling were mirrored at the cellular level. Downregulation of endogenous RasGRP3 inhibited cell proliferation, impeded cell migration and reduced colony formations in soft agar. Our results suggest that RasGRP3 may provide an addition targetable signaling element in lung cancer. Citation Format: Jing Yang, Timothy Esch, Dazhi Yang, Peter Blumberg. RasGRP3 contributes to Ras signaling, growth, and migration of human lung cancer cell lines. [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 4292. doi:10.1158/1538-7445.AM2013-4292
CLINICAL PRESENTATION, MANAGEMENT AND PROGNOSIS OF PATIENTS WITH SPONTANEOUS CORONARY ARTERY DISSECTION
Authors: Vedant Pargaonkar, Abha Khandelwal, Gomathi Krishnan, Katharine Sears, Valerie Hoover, William Fearon, David Lee, Alan Yeung, Sandra Tsai, Mary Nejedly, Sahar Naderi, Jennifer Tremmel
Journal: Journal of the American College of Cardiology (2016)