tbuckley/cabot-search huggingface dataset:
Abstract 2026: MicroRNA-214 is a negative regulator of p53
Authors: Hua Yang, William Kong, Kendra Williams, Lili He, Jin Q. Cheng
Journal: Cancer Research (2010)

Abstract The p53 transcription factor mediates multiple cellular functions including the response to genotoxic stress, differentiation, cell cycle and apoptosis. Since p53 inactivation is a critical event in tumor development, the regulation of p53 and its pathway is of prime importance in the understanding of tumorigenesis. While a number of microRNAs have been shown to be regulated by p53, microRNA regulation of p53 is still not well documented. Here we demonstrate that miR-214, a putative oncogenic miRNA, regulates p53 protein but not mRNA level by direct targeting 3′UTR of p53. Ectopic expression of miR-214 represses p53 and enhances the resistance to radiation- or chemotherapeutic agent-induced cell cycle arrest and apoptosis in wild-type but not mutated p53 cells. Introduction of p53 cDNA lacking 3′UTR largely abrogates miR-214-induced cell growth and survival. Depletion of endogenous miR-214 elevates protein level of p53 and induces apoptosis in human cancer cell lines expressing wild-type p53. These findings indicate that miR-214 is an important posttranscriptional regulator of p53 and exerts its oncogenic activity through targeting p53. 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 2026.
FRI0092 Lung Disease among Rheumatoid Arthritis Patients – Results from Ontario BIOLOGICS Research Initiative (OBRI)
Authors: S. Mittoo, B. Jacob, C. Bombardier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Lung disease (LD) is a major, extra-articular complication and co-morbid condition among patients with rheumatoid arthritis (RA). Many disease-modifying agents (DMARDs) have safety concerns when used in the treatment of RA patients with chronic lung disease. <h3>Objectives</h3> To describe the clinical characteristics of RA patients with LD in a population-based cohort and compare patterns of DMARD use at baseline among patients with and without LD. We also sought to evaluate the difference in clinical outcomes of RA patients with and without LD at 1-year follow-up. <h3>Methods</h3> Patients with RA were recruited from the Ontario Best Practice Research Initiative (OBRI), a clinical registry of early and established RA patients followed in routine care. This is an analysis of a prospective cohort of adult patients with a physician-diagnosis of RA who had at least 1 swollen joint. Lung disease was defined as the presence of interstitial lung disease (ILD), pulmonary embolism (PE), chronic obstructive airway disease (COPD), asthma, and other lung disorders. Patients without LD were considered those who did not have LD at baseline or at their last follow-up study visit. Clinical characteristics between RA patients with and without LD were compared using t-test and chi-squared. <h3>Results</h3> Among 2,328 patients, 286 (12%) had LD and 1802 (86%) did not. Of those with LD, 123 (43%) had asthma, 64 (22%) had COPD, 53 (19%) had ILD, and 8 (3%) had PE and/or other LD. At baseline, RA patients with LD were significantly older in age (62.3±11.9) years compared to those without LD (56.3±12.8 years) (p≤0.001). Majority (78%) were female with a mean disease duration of 8.6 years. LD patients had higher ESR and CRP values at baseline, but tender and swollen joint counts did not significantly differ. LD patients were more frequently treated with BIOLOGICS (9.9% vs 5.1%, p&lt;0.05), but received less methotrexate (50.4% vs 59.0%, p&lt;0.05) compared to non-LD patients. At 1-year follow-up, RA patients with LD compared to those without LD had significantly greater number of tender joints (mean ± SD of 4.0±6.1 and 2.7±4.4, p=0.03), higher ESR (26.1±21.4), greater DAS28 scores (p=0.04), and higher levels of HAQ (p=0.02). <h3>Conclusions</h3> Despite same disease activity at baseline, lung disease patients had higher DAS28 scores compared to without lung disease at 12 months. The factors that contribute to discrepancy and the reasons for the worse disease activity needs to be explored further. <h3>Acknowledgements</h3> OBRI Investigators <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5713
A Rare Case of Tolosa-Hunt Syndrome Imaged With FDG PET/CT and MRI
Authors: Yu-Chin Wu, Te-Chun Hsieh, Chia-Hung Kao, Yen-Liang Liu, Kuo-Yang Yen, Shung-Shung Sun
Journal: Clinical Nuclear Medicine (2011)

We report on the imaging findings of Tolosa-Hunt syndrome in a 59-year-old patient. Clinical findings included periorbital pain, ptosis, disordered eye movements, and blurred vision. Treatment with intravenous administration of steroid resolved all symptoms. Currently, magnetic resonance imaging plays a key role in the diagnosis of Tolosa-Hunter syndrome for locating the inflammatory tissue and follow-up. This case of Tolosa-Hunter syndrome with representative (FDG PET/CT) images may imply that FDG PET/CT is a useful tool in detecting and monitoring of this disease.
Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons
Authors: Samuel M. Cohen, Huan Ma, Kishore V. Kuchibhotla, Brendon O. Watson, György Buzsáki, Robert C. Froemke, Richard W. Tsien
Journal: Neuron (2016)
The triplet docetaxel, carboplatin and capecitabine in recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN)
Authors: J. Kattan, F. Farhat, G. Chahine, F. Nasr, W. Moukadem, F. Younes, M. Ghosn
Journal: Journal of Clinical Oncology (2005)

5585 Background: Despite recent advances in surgery and radiotherapy for SCCHN, the prognosis remains dismal once relapsed or metastatic. Phase I and II trials with combination of three-weekly-Taxotere, Cisplatin and 5-days 5-FU-continuous infusion in the treatment of recurrent or metastatic SCCHN showed very promising results, according to the literature. In an attempt to enhance the safety and/or the activity of this triplet, we performed a phase II trial combining weekly Docetaxel and weekly Carbopatin to oral 5-FU (Capecitabine). Methods: Patients fitting inclusion criteria were included and received: Docetaxel 25 mg/m2 and Carboplatin (AUC = 2) d1 d8, and Capecitabine 1350 mg/m2/d d1–14. Treatment was repeated every 3 weeks. Primary objectives were determination of response rate and toxicity profile. Time till progression, response duration and overall survival were the secondary objectives. Results: From January 2002 through November 2004, 21 patients were included: 6 pts with metastatic disease and 15 with loco-regional disease. The primary tumor was larynx in 19 and oropharynx in 2 pts. 7 pts were previously untreated, 11 had surgery and/or radiotherapy, and 3 had received chemo radiation. Median age was 62 (extremes: 40 - 75). Sex ratio was 4:1. 125 cycles were delivered with a mean of 6 cycles/pt (extremes: 1 -9). There were 1 CR and 8 PR (43%). There were 2 SD lasting 3 and 10 months respectively. Median time to progression was 4.2 months (extremes: 1–14). Response duration was 4.6 (extremes: 1 + - 11). After a median follow-up of 17 months, 6 pts remains alive. Main toxicities (grade 3/4) were: anemia and thrombocytopenia in 2 pts each. Conclusion: This combination according to our schedule was remarkably safe and extremely tolerated. Its efficacy was comparable to the literature and needs further investigation. No significant financial relationships to disclose.
THU0118 Toll-Like Receptor Dependent Autoantigens in Animal Models and Humans in Use to Improve Collagen Induced Arthritis
Authors: B. Marklein, C. Grimm, G.-R. Burmester, K. Skriner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current therapies for autoimmune diseases still mainly suppress inflammation and only indirectly affect antigen-specific immune activities. Therapeutically targeting relevant autoantigens found in humans and animal models of RA has the potential to deliver maximal efficacy with minimal adverse effects. <h3>Objectives</h3> This study was conducted with sera from patients with rheumatoid arthritis, systemic lupus erythematosus as well as with arthritis and lupus-like disease animal models to identify identical autoantigens in human and animal models for disease modifying use. <h3>Methods</h3> Using protein filter technology (28000 human protein filter) the autoantigen profile of RA and SLE patients, mouse collagen and zymosan induced arthritis, as well as collagen and pristan induced arthritis in rats and TLR7, TLR9 deficient double-deficient and MyoD88 and Tir8 deficient mice of the MRL-lpr/lpr background were obtained. Cationic liposomes transferring siRNAs were used for the validation of their potential as therapeutic target in collagen induced arthritis in mice (CIA). <h3>Results</h3> By high throughput methods using proteins filters, over 200 clones were identified to bind patient, mouse and rat autoantigens. We could identify that up to 90% of all autoantigens including anti-histone, snRNPs, hnRNP, t-RNA synthetases, PM, Scl2, HSP proteins, and 17 different ribosomal autoantigens are MyoD88 dependent and influenced by Tir8. We found 18 identical proteins targeted in human and animal situations of arthritis. In contrast, autoantigens such as citrullinated proteins are generated independently of MyoD88 Toll7, 9 and Tir8. Systemic administration of siRNAs in CIA mice inhibiting expression of Toll dependent autoantigens were used for the validation of their potential as therapeutic target in RA. These novel data indicate that nucleic acid-binding proteins are targeted in animal models and patients with RA. Systemic blocking of common RNA or DNA binding proteins overexpressed in synovial target tissue appears to modify arthritis. <h3>Conclusions</h3> These novel data indicate that nucleic acid-binding proteins are targeted in animal models and patients with RA. Systemic blocking of common RNA or DNA binding proteins overexpressed in synovial target tissue appears to modify arthritis. <h3>Disclosure of Interest</h3> None Declared
Abstract 5035: Stable transfection of the osteosarcoma cell line SaOs2, genetically transformed MSCs and osteoblasts with insulin-like growth factor 2 receptor.
Authors: Huayi Qu
Journal: Cancer Research (2013)

Abstract Osteosarcoma (OS) is the most commonly seen primary malignant bone tumor in children and adolescents. With neo-adjuvant chemotherapy and other treatment regimens developed, event-free survival has increased to 70%, but the prognosis remains poor for those patients with unresectable or metastatic tumors or less responsive tumors. Insulin-like growth factor 2 (IGF2) and its receptor (IGF2R) are known to be over-expressed in several cancers including OS and have roles in regulating cellular growth and proliferation. Although IGF2R is thought to be a tumor suppressor, the research results in different experimental systems are variable. Our recent studies have demonstrated that IGF2R is consistently over-expressed, relative to other known transmembrane receptors on the cell surface across, 4 standard and 10 patient-derived OS cell lines. To further elucidate the effects of IGF2R in OS, the OS cell line SaOS2 and two cell lines which were genetically transformed, as follows; mesenchymal stem cells (MSC) and osteoblasts (OB) with human telomerase reverse transcriptase and SV40Tag (MSC-TS and OB-TS) were transformed with IGF2R by lentiviral transfection. Drug resistant colonies were picked up 21 days after selection to obtain stably transfected SaOS2, MSC-TS, and OB-TS cell lines now named, SaI, MSC-TSI and OB-TSI, respectively. After cloning, the highest and the lowest IGF2R expression clones were selected from these different cell lines via real-time PCR and western blot for further analysis. The comparison between the lines and characterizations are underway. Initial results suggest introduction of IGF2R changes the phenotype by enhancing cellular motility. Further studies will be presented and include the following: 1) cell proliferation assays, 2) motility and migration assays, 3) subcutaneous tumorigenicity assays, 4) expression profiling, and 5) differentiation assays. In the context of osteosarcoma introduction of IGF2R enhances motility, which is unexpected given prior expectations based on the non-signaling nature of this receptor. Citation Format: Huayi Qu. Stable transfection of the osteosarcoma cell line SaOs2, genetically transformed MSCs and osteoblasts with insulin-like growth factor 2 receptor. [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 5035. doi:10.1158/1538-7445.AM2013-5035
Abstract 1102: Regulation of protein citrullination through p53/PADI4 network in DNA damage response
Authors: Koichi Matsuda, Chizu Tanikawa, Yusuke Nakamura
Journal: Cancer Research (2010)

Abstract Upon wide range of cellular stresses, p53 is activated and inhibits malignant transformation through the transcriptional regulation of its target genes related to apoptosis, cell cycle arrest, and DNA repair. However its involvement in post-translational modifications of proteins has not been well characterized so far. We here report the novel role of p53 in the regulation of protein citrullination. Citrullination (also referred as deimination) is one form of PTMs converting an arginine residue in protein to a citrulline residue. This reaction is mediated by a Ca2+-dependent enzyme called as peptidylarginine deiminase. Citrullination of proteins results in a loss of positive charge and causes a significant biochemical change. On the other hand, citrullinated peptides/proteins are recognized as a non-self protein and subsequently activate immune systems. Hence, protein citrullination is now considered to play a pivotal role in various human diseases, but any roles of citrullination in carcinogenesis were not reported so far. We found p53 transactivated peptidylarginine deiminase type 4 (PADI4) through intronic p53-binding site and ectopic expression of p53 or PADI4 induced protein citrullination. In addition, various proteins were citrullinated in response to DNA damage, but knockdown of PADI4 or p53 remarkably inhibited their citrullination, indicating the regulation of protein citrullination in a p53/PADI4 dependent manner. We identified that PADI4 citrullinated histone chaperon protein, nucleophosmin (NPM1) at arginine 197 residue in vivo under physiological condition. NPM1 was shown to continuously shuttle between the nucleus and cytoplasm and translocate from nucleoli to nucleoplasm as a response to DNA damage. Therefore, we investigated the effect of protein citrullination on subcellular localization of NPM1. Immunocytochemical analysis revealed that citrullination of NPM1 by PADI4 resulted in its translocation from nucleoli to nucleoplasm, while PADI4 did not alter the localization of mutant NPM1 (R197K). Furthermore, ectopic expression of PADI4 inhibited tumor cell growth, and concordantly knockdown of PADI4 attenuated p53-mediated growth inhibitory activity, demonstrating the significance of PADI4-mediated protein citrullination in the p53 signaling pathway. Most of previous studies assessing enzymatic activities of PADIs were conducted under non-physiological condition using Ca ionophore or at higher Ca concentration. To our knowledge, this is the first report demonstrating the physiological regulatory mechanism of protein citrullination. Thus, p53 that can directly or indirectly modulate biological property of various proteins through the protein citrullination. 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 1102.
Whole-Body FDG PET/CT in Diagnosis of Internal Mammary Nodal Metastasis of Ovarian Carcinosarcoma
Authors: Yu-Wen Chen, Chia-Yang Lin, Po-Nien Hou, Chuan-Shiaw Lee, Ming-Feng Hou, Eing-Mei Tsai
Journal: Clinical Nuclear Medicine (2011)

Internal mammary lymph node is rare metastatic site in ovarian neoplasm. In this study, we report an ovarian carcinosarcoma with peritoneal carcinomatosis initially. Annually, whole-body FDG PET/CT is indicated during 4 years. Tiny peritoneal nodules are found on the first-time FDG PET/CT imaging. A high grade of FDG-avid internal mammary nodal activity is shown on the secondary time of FDG PET/CT imaging. Pathologic result of excision biopsy demonstrates carcinoma metastasis. On the recent imaging, significant FDG-avid peritoneal and subphrenic carcinomatosis has happened again. After surgery and chemotherapy, the patient is still followed up in clinic.
SAT0144 Can rheumatoid arthritis (RA) incomplete secondary responders to TNF-alpha attain an efficacious and safe response by switching to certolizumab pegol?:
Authors: M. Schiff, R. Goldblum, J. Tesser
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Certolizumab pegol (CZP), an inhibitor of TNF-alpha, has demonstrated rapid and sustained efficacy in RA patients in multiple clinical trials and is approved for the treatment of RA in many countries. Switching from one anti-TNF therapy to another has been investigated in many open-label uncontrolled studies, but in few controlled trials. <h3>Objectives</h3> This double blind (DB) controlled study was to examine the effect of 12 weeks treatment with CZP or placebo on measures of disease activity in patients with RA on stable concomitant methotrexate (MTX) or other non-biologic therapy and who had discontinued a TNF-alpha inhibitor other than CZP. <h3>Methods</h3> This randomized, multi-center, DB, parallel group 12-week study randomized (2:1 ratio) 37 subjects who were secondary non-responders (primary non-responders were excluded) or intolerant to TNF-alpha inhibitors to either CZP (27 subjects) or placebo (10 subjects) in addition to background MTX or other DMARDs. Subjects were required to washout from previous TNF inhibitors for at least 4 weeks. CZP was administered subcutaneously in approved doses. After the Week 12 visit, all subjects could participate in an open-label phase with CZP dosing for an additional 12 weeks (to be reported at a later date). (NCT01147341). <h3>Results</h3> Of the 37 subjects who were randomized for safety, 35 (26 on CZP and 9 on placebo) were in the Efficacy Population (completed at least 4 weeks of dosing). Demographic/baseline characteristics of the 2 treatment groups were similar: average age 56 vs 59 years, mean disease duration 12 vs 14 years, mean MTX dose 16.4 vs 16.1 mg/week, #TNF failed 1.40 vs 1.33 and DAS 5.48 vs 5.44 (placebo vs active). Adverse events occurred in 16/27 (59.3%) CZP subjects and 4/10 (40%) placebo subjects. There were no serious adverse events, deaths, neoplasms, opportunistic or serious infections. <h3>Conclusions</h3> In this double-blind controlled 12-week study in incomplete secondary responders to TNF-alpha inhibitors, statistically significant efficacy with CZP compared to placebo was observed for both primary efficacy endpoints and most secondary endpoints. The ACR 20 response rate observed with CZP (61.5%) is higher than that reported in most previous studies of incomplete TNF responders. In addition, CZP demonstrated good safety and tolerability. This study supports the use of CZP in RA patients who are secondary non-responders to TNF inhibitors or intolerant to them. <h3>Disclosure of Interest</h3> M. Schiff Grant/Research support from: UCB, R. Goldblum: None Declared, J. Tesser Consultant for: UCB. This is an investigator initiated study.
Abstract 988: Upregulation of pyruvate dehydrogenase kinase 3 mediates hypoxia-induced drug resistance in colon cancer
Authors: Chun-Wun Lu, Shao-Chieh Lin, Chun-Wei Chien, Shih-Chieh Lin, Bo-Wen Lin, Jenq-Chang Lee, Shaw-Jenq Tsai
Journal: Cancer Research (2011)

Abstract Colorectal cancer is the second leading cause of cancer-related death in both male and female worldwide. Despite the efforts of screening and advances in treatment, 50% of patients with colon cancer will ultimately die from their disease. One major hurdle of treating colon cancer is its high recurrence due to resistance to anti-cancer therapy of hypoxic tumor, a survival advantage resulting from metabolic switch of cancer cells. The switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and is associated with tumor malignancy. Previous studies demonstrated that pyruvate dehydrogenase kinase-1 (PDK1) and PDK3 play an important role in the metabolic switch of cancer cells. Herein, we assessed the expression profile of PDK1 and PDK3 in colorectal cancer. Western blotting results demonstrated that levels of PDK3 were markedly upregulated in colon cancer compared to adjacent normal tissues while levels of PDK1 were decreased in cancer cells. Immunohistochemical staining (n=307) further revealed that expression of PDK3 was positively correlated with the level of hypoxia inducible factor-1α (HIF-1α) and the severity of cancer. Level of PDK3 was markedly induced by hypoxia in a HIF-1α dependent manner, while HIF-2α had no effect on PDK3 expression in colon cancer cell lines. Aberrant expression of PDK3 mediates hypoxia-induced drug resistance as knocking-down PDK3 by siRNA under hypoxia abolished such protective effect. Taken together, these data demonstrated that PDK3 is overexpressed in colon cancer and is associated with tumor malignancy. Our current findings provide novel insights about metabolic switch in cancer cells and suggest that PDK3 can be a new and pivotal target for cancer therapy. 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 988. doi:10.1158/1538-7445.AM2011-988