tbuckley/cabot-search huggingface dataset:
Hypertrophic Cranial Pachymeningitis With IgG4-Positive Plasma Cells Detected by C-11 Methionine PET
Authors: Takashi Norikane, Yuka Yamamoto, Masaki Okada, Yukito Maeda, Fumitoshi Aga, Nobuyuki Kawai, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2011)

A 53-year-old man who presented with mild headache and ophthalmodynia underwent carbon-11 methionine (MET) positron emission tomography (PET). MET PET images demonstrated intense uptake in the periphery of the brain, significantly higher than the physiological uptake in the brain. Biopsy specimens from the pachymeninx indicated hypertrophic pachymeningitis with IgG4-positive plasma cells. After steroid therapy, he became asymptomatic, and a follow-up PET scan showed disappearance of the peripheral brain uptake of MET.
Abstract 2021: MicroRNA affinity assay
Authors: Miao Shi, Weiguo Han, Simon Spivack
Journal: Cancer Research (2010)

Abstract Introduction: MicroRNAs (miRNAs) are small noncoding RNAs functioning in gene regulation. In animal cells, miRNAs bind to target sites in the 3’ UTR of mRNAs, causing posttranscriptional repression or degradation of mRNAs. The identification of specific miRNAs to target a 3′UTR of a given gene is essential for studies in gene regulation. However, the sequence software programs conventionally used to predict binding of individual microRNAs to a given mRNA transcript are notoriously unreliable, and specific microRNA-mRNA binding is very difficult to directly affirm using currently available techniques. We have developed a microRNA affinity assay that addresses this need. Methods: We chose a candidate gene that had been extensively studied experimentally for microRNA regulation; it is known that miR-200c and miR-200b can bind to 3′UTR RNA of TCF8 [Hurteau 2007]. Here, a 500bp fragment of the 3′UTR RNA of TCF8 was generated by IVT, and used as a bait sequence to identify miRNAs that bind a mixture of known miRNA composition, and alternately a naturally produced cellular miRNA pool. After separation, miRNA qPCR was used to check recovery rate of miRNA, and cloning and sequencing was used to identify miRNAs. Results: Specific miRNAs from a synthetic mixture miRNAs, miRNA qPCR results displayed excellent recovery rates (151.57% with pipetting error, for miR-200c), 88.88% for the closely related miR-200b, 0.31% for the sequence-unrelated miR-9, 0.67% (miR-10a), 0.1% (miR-20a), 8.78% (miR-34a with some 3′UTR homology), 0.11% (miR-100), 0.16% (miR-140-5p), 0.98% (miR-144), 0.33% (miR-802) and 1.58% (miR-1234). After cloning the captured miRNAs, there were 10 sequences from miR-200c, 7 sequences from miR-200b, and one other sequence in 18 sequenced clones. When separating specific miRNAs from naturally produced NHBE cell miRNA pool, miRNA qPCR results show that their recovery rates are 88.88% (miR-200c), 80% (miR-200b), 0.07% (miR-20a), less than 0.006% (miR-34a) and 0.01% (miR-100). Conclusions: For both simple known and complex unknown microRNA pools, this pull-down strategy is effective in determining microRNA-mRNA binding. In future work, we will use other 3′UTR RNA sequences of candidate genes as bait sequence, for microRNA-related discovery and confirmation. 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 2021.
AB0283 Dermatologic adverse events in a cohort of patients with rheumatoid arthritis using anti-tnf therapy in a real-life setting
Authors: A. P. Real, A. Palomino, L. Villarreal, J. Bello, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biological therapy is a major therapeutic tool to prevent clinical and radiological progression of rheumatoid arthritis (RA). On the other hand, adverse effects of these medications are a problem in clinical practice. <h3>Objectives</h3> The aim of this study was to describe and compare the most frequent dermatologic adverse events with the use of biologic anti-TNF therapy in patients with RA in a real-life ambulatory setting. <h3>Methods</h3> A descriptive study was done. A review of dermatological adverse event reports presented in pharmacovigilance committee was completed monthly during last 12 months in a specialized in RA center in Colombia. Descriptive epidemiology was used, percentages and averages were calculated. <h3>Results</h3> 357 patients were using biological therapy in a cohort of 1678 RA patients last 12 months. Were 314 women (87.9%) and 43 (12.1%) men. Mean age 56.4 years old. In 31 (8.7% of all) patients were reported dermatologic adverse events (AE); AE were categorized according WHO classification in mild, moderate and severe; between them 14 (45.2%) were mild, 17 (54.8%) were moderate and none were severe. From 31 events reported, only 7 (22.6%) were biopsied and the other 24 cases were not clarified what type of dermatologic reaction presented (77.4%). For time of presentation, in first 15 days were informed 8 AE (25.8%), between 15 to 30 days were 6 (19.4%) AE, and more than 30 days were reported 17 (54.8%) AE. Regarding therapeutic approach in 5 patients (16.1%) biologic was temporarily suspended, in 14 (45.2%) was permanently withdrawn and patients were switched to another biological, and 12 (38.7%) patients were followed for drug and reactions surveillance. Concerning to type of biologic in 29 patients (93.5%), dermatologic adverse events were with anti-TNF therapies. <h3>Conclusions</h3> Dermatological adverse events using biologics founded in patients of a specialized RA center are similar to those reported in literature; Biological therapy is considered a safe and recommended treatment for management of RA. Dermatologic AE were more mostly common with anti-TNFs therapies. <h3>Disclosure of Interest</h3> None Declared
Longitudinal Tibial Fatigue Fracture
Authors: RODNEY V. POZDERAC
Journal: Clinical Nuclear Medicine (2002)

Purpose The author reports three cases of longitudinal tibial fatigue fractures, reviews the literature, and discusses characteristic features that suggest the diagnosis may be made by bone scintigraphy. Methods Radiographs and two- or three-phase bone scintigraphs with Tc-99m MDP were obtained in three runners who had exercise-related leg pain and whose clinical symptoms suggested either stress fractures or shin splints. The literature was reviewed and previously reported scintigraphic findings were compared with those seen in these three cases. Results In contrast to the focal, elliptical, cortex-based abnormal activity usually seen in the upper or middle tibia in patients with tibial stress fractures, all three patients had a long area of abnormal diffusely increased tibial activity that extended from the tibiotalar region proximally. This finding was seen on the 3-hour delayed static images of all three patients and was suggested on the blood-pool (tissue phase) images. The literature also contained reports of these same scan characteristics. Radiographs subsequently disclosed a longitudinal tibial stress fracture in one patient, computed tomography was positive in the second patient, and findings of clinical follow-up and radiographs were consistent with this diagnosis in the third patient. Conclusion In the appropriate clinical setting and with normal or nondiagnostic radiographs, the presence of a long area of diffusely increased activity in the distal tibia extending proximally from the tibiotalar junction is indicative of a longitudinal fatigue fracture.
Abstract 5190: GnRH promotes peritoneal adhesion and dissemination of ovarian cancer cells
Authors: Lydia W. T. Cheung, Peter C. K. Leung, Alice S. T. Wong
Journal: Cancer Research (2010)

Abstract Ovarian cancer has the highest mortality of all gynecological cancers. It is often diagnosed at a late stage characterized by widespread peritoneal dissemination and malignant ascites. A key initial step in metastasis is the adhesion of ovarian cancer cells to the peritoneal mesothelium and extracellular matrix (ECM). Gonadotropin-releasing hormone (GnRH) receptor is present in 80% of ovarian carcinomas and its role in ovarian cancer cell migration/invasion has recently been revealed. Here, we show for the first time a role for GnRH in promoting ovarian cancer cell adhesion to the peritoneum. We observed that GnRH agonist (GnRHa)-stimulated cells were able to adhere to the peritoneal mesothelium efficiently. Moreover, the expression of integrins (α2, α5 and β1) in ECM recognition for collagen I, laminin, and fibronectin were upregulated and activated by GnRHa. The adhesion of ovarian cancer cells to the mesothelium/ECM components activated by GnRHa could be blocked by neutralizing antibodies to α2, α5 and β1 integrin. Knockdown of the GnRH receptor using small interfering RNA significantly abrogated the GnRH-induced cell adhesion and integrin expression, confirming that these effects were GnRH receptor specific. Furthermore, we showed that downregulation of β1 integrin and GnRH receptor with short hairpin RNA-mediated gene silencing significantly reduced ascites formation and intra-abdominal metastasis in intraperitoneal xenografts of human ovarian cancer in nude mice. These results indicate that GnRH may play a critical role in the peritoneal adhesion and dissemination of ovarian carcinomas and could be a promising target in ovarian cancer (This work is supported by the Hong Kong Research Grants Council Grant HKU778108 to A.S.T.W.). 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 5190.
Abstract 1944: Evaluation of the prognostic value of miRNA-181b and its target identification and validation in colorectal cancers.
Authors: Liselle Bovell, Balananda-Dhurjati K. Putcha, Divya Devadasan, Sejong Bae, William E. Grizzle, Upender Manne
Journal: Cancer Research (2013)

Abstract Background: microRNAs (miRNAs) are 19 to 24 nucleotide sequences that regulate cell proliferation, differentiation, and apoptosis. miRNA-181b is involved in tumor initiation and progression of several human malignancies including colorectal cancers (CRCs). Thus, we sought to determine the prognostic value of miRNA-181b in CRCs. Methods: Expression of miRNA-181b was quantified, by quantitative PCR (q-RT-PCR), in normal (benign colonic epithelia) tissues and in their corresponding CRC archival tissue samples collected from 345 patients. The expression levels were correlated with patient overall survival. Putative molecular targets of miRNA-181b were identified by in silico analysis. miRNA-181b mediated, post-transcriptional regulation of these targets was assessed in CRC cell lines (SW480, HCT116 p53-/- and HCT116 +/+) by transfection studies. The targets were validated by measuring their mRNA expression levels, by use of qRT-PCR, in CRC tissues that exhibited elevated levels of miRNA-181b as well as by cloning techniques to assess a direct interaction between miRNA-181b and 3’UTRs of its target genes using luciferase assays. Results: Survival analysis indicated that increased expression of miRNA-181b was associated with poor prognosis for CRCs (log rank, p=0.004). Fourteen putative molecular targets of miRNA-181b were identified by in silico analysis, and miRNA-181b mediated post-transcriptional regulation of these targets was validated in CRC cell lines by q-RT-PCR. Integrin alpha-3 was up-regulated, and BCL2LII and TNFα were down-regulated upon overexpression of miRNA-181b in vitro. Also, these targets were validated in CRC tissues that exhibited elevated miRNA-181b levels. The direct interaction of miRNA-181b with the target gene 3’UTRs was validated with luciferase assays. Conclusions: These findings demonstrate that miRNA-181b regulates expression of Integrin alpha-3, BCL2LII, and TNFα; and is a prognostic marker for colorectal cancers. Citation Format: Liselle Bovell, Balananda-Dhurjati K. Putcha, Divya Devadasan, Sejong Bae, William E. Grizzle, Upender Manne. Evaluation of the prognostic value of miRNA-181b and its target identification and validation in colorectal cancers. [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 1944. doi:10.1158/1538-7445.AM2013-1944
THE IDENTIFICATION OF CORONARY ATHEROSCLEROSIS IS ASSOCIATED WITH INITIATION OF PHARMACOLOGIC AND LIFESTYLE PREVENTIVE THERAPIES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ankur Gupta, Ravi Varshney, Emily Lau, Edward Hulten, Marcio Bittencourt, Michael Blaha, Roger Blumenthal, Matthew Budoff, Craig Umscheid, Khurram Nasir, Ron Blankstein
Journal: Journal of the American College of Cardiology (2016)
Quality of life in relation to hormonal treatment of postmenopausal women in the Dutch Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial.
Authors: JG van Nes, DW Voskuil, FE van Leeuwen, JM Junggeburt, HC de Haes, CJ van de Velde
Journal: Cancer Research (2009)

Abstract Abstract #21 Background In the last decade, use of adjuvant hormonal treatment increased as well as its duration. Aromatase inhibitors are associated with a minimal increase of disease free survival compared to tamoxifen. Both therapies are associated with different side effects which can affect quality of life (QoL). Therefore, it is necessary to compare the QoL of patients using these therapies. We compared the QoL of women participating in the Dutch Tamoxifen Exemestane Adjuvant Multicentre (TEAM) Trial.&amp;#x2028; Patients and Methods The Dutch TEAM trial included 2754 postmenopausal early breast cancer patients who were randomised between five years of exemestane or 2.5-3 years of tamoxifen followed by 2.5-2 years of exemestane. A total of 742 patients were invited onto the QoL subprotocol. At one (T1) and two (T2) years after start of hormonal treatment, patients were ask to fill in questionnaires. This questionnaire contains the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and the EORTC BR23 questionnaires, supplemented with Functional Assessment of Cancer Therapy - Endocrine Subscale (FACT-ES) questions covering endocrine symptoms. The endpoint was the difference in QoL between patients receiving tamoxifen or exemestane.&amp;#x2028; Results Questionnaires were completed by 543 patients at T1 and 83% of these returned the questionnaire of T2. There were no significant differences in physical functioning, role functioning, cognitive functioning, emotional functioning, body image, breast symptoms, arm symptoms and endocrine symptoms between both treatment groups at T1 nor at T2. Patients receiving exemestane had significantly less sexual enjoyment (difference of 9 points on a 0-100 scale; p=0.004) and more insomnia (difference of 8 points; p=0.005) compared to patients receiving tamoxifen at T1. At T2, there was no statistically significant difference in sexual enjoyment (difference of 4 points; p=0.287). However, patients receiving exemestane reported significantly worse sexual functioning (difference of 5 points; p=0.020) and still more insomnia (difference of 8 points; p=0.004).&amp;#x2028; Conclusion Patients using exemestane reported less sexual enjoyment and more sexual functional problems than patients using tamoxifen. This may be explained by the fact that specific side effects of exemestane (e.g. vaginal dryness) can cause less sexual enjoyment which can result in a decreased sexual functioning. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 21.
NEUROCARDIAC INJURY IN PATIENTS WITH SUBARACHNOID HEMORRHAGE IS ASSOCIATED WITH REGIONAL LEFT VENTRICULAR DISCOORDINATION
Authors: Zhi Qi, Masataka Sugahara, Elizabeth A. Crago, Yuefang Chang, Theodore F. Lagattuta, Khalil Yousef, Robert M. Friedlander, Marilyn T. Hravnak, John Gorcsan
Journal: Journal of the American College of Cardiology (2016)
Abstract P2-01-08: Different numbers and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes.
Authors: DJ Peeters, P-J van Dam, H Wuyts, GG Van den Eynden, K Jeuris, A Prové, A Rutten, M Peeters, P Pauwels, SJ Van Laere, J Hauspy, PA van Dam, PB Vermeulen, LY Dirix
Journal: Cancer Research (2012)

Abstract Introduction: The enumeration of circulating tumour cells (CTCs) with the EPCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). However, breast cancer has been shown to be a molecularly heterogeneous disease. The aim of this study was to assess potential differences in the detection and prognostic significance of CTCs according to the immunohistochemically defined molecular subtypes of breast cancer. Methods: CellSearch CTC counts were obtained from 110 patients with MBC prior to first line systemic treatment, treated at GZA Hospitals Sint-Augustinus between november 2007 and december 2011. Clinicopathological variables were prospectively entered in a database. Based on the St-Gallen surrogate definitions of intrinsic breast cancer subtypes (Goldhirsch et al. Ann Oncol 2011), patients were divided in 5 groups: luminal A (ER/PR+, HER2−, Bloom-Richardson histological grade I-II), luminal B – HER2 negative (ER/PR+, Her2−, grade III), luminal B – HER2 positive (ER/PR+, HER2+, any grade), HER2 positive – non luminal (ER/PR−, HER2+), and triple negative (TN) (ER/PR−, HER2−). Differences in progression free survival (PFS) and overall survival (OS) according to the FDA approved prognostic cut-off of ≥5 CTC/7.5 ml blood were estimated using Kaplan Meier and Cox proportional hazard statistics. Results: CTC were detected in 78 of 110 (71%) patients. Higher detection rates and numbers of CTC were observed in patients with luminal A and TN breast cancer as compared to patients with luminal B and HER2 positive disease. However, no differences in positivity rates were observed between molecular subtypes according to the 5 CTC prognostic cut-off point (table 1). After a median FU time of 3.1 years, 39 patients had died. In the total study population, the presence of ≥5 CTC was an independent predictor of PFS and OS in multivariate analysis (PFS: HRCTC≥5=2.236 (1.366–3.658), p = 0.001; OS: HRCTC≥5=3.180 (1.553–6.509), p = 0.002). When analyzing subgroups separately, a lower prognostic power was observed in the HER2 positive and luminal B subgroups. Conclusion: Significant differences were observed in the detection and prognostic significance of EPCAM positive CTC according to the immunohistochemically defined breast cancer subtypes. Interestingly, CTC were detected more frequently in patients with luminal A and TN tumors. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2 positive patients with MBC. Our data independently confirm those reported by Giordano et al. (Ann Oncol 2010) in a large clinically uniform population of patients with MBC before the start of first-line treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-08.
Cutaneous Wound Healing
Authors: Adam J. Singer, Richard A.F. Clark
Journal: New England Journal of Medicine (1999)

The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Every year in the United States more than 1.25 million people have burns1 and 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.2 The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar. Recent advances in cellular and molecular biology have greatly expanded our understanding . . .
Abstract 3672: Adrenocortical carcinoma cell lines are sensitive to compounds targeting the G2/M transition
Authors: Erica Datrup, Michael J. Demeure, Kimberly J. Bussey
Journal: Cancer Research (2010)

Abstract Adrenocortical carcinoma (ACC) is an aggressive tumor of the adrenal cortex. It affects 1-2 per million and has a 5 year survival rate of 25-30% due to late detection and a lack of effective systemic therapy. Mitotane, an isomer of the insecticide DDT, is the only compound approved for the treatment of patients with ACC. It has a poor response rate (22% as a single agent) and a toxicity profile that often results in dose reduction or cessation of therapy altogether. New therapies are desperately needed. Expression profiling of ACC by ourselves and others highlights the importance of the G2/M transition, the p53 pathway, and signaling of IGF2 through IGF1R. Using this knowledge, we profiled the in vitro chemosensitivity of the two ACC cell lines, H295R and SW-13, to compounds that target aspects of these pathways. Cells were plated, and drug added 24 hours later in a 3-fold serial dilution, with the exception of mitotane which was done as a 1.5-fold serial dilution. Viability was assessed by CellTiter Glo at 3 different time points. The cell lines show sensitivity to compounds that target the G2/M transition (VX-680 and BI-2536) and EGFR (erlotinib). The difference in response between H295R and SW-13 to LY294002 suggests the cell lines harbor a difference in the relative contributions of PI3K signaling versus Ras-Raf-MEK signaling downstream of IGF1R. Additionally, the response of both cell lines to erlotinib suggests that EGFR signaling may play a role in ACC. Neither cell line was particularly sensitive to MDM2 inhibition, indicating that this is not a good target to restore p53 pathway function. Finally, our results suggest that further testing of compounds that target G2/M is warranted, particularly PLK-1 inhibitors.In vitro chemosensitivity profiling in ACC cell linesCompoundMechanism of ActionTime PointAverage IC50 for SW-13 in uMAverage IC50 for H295R in uMMitotaneUnknown, but results in mitochondrial degeneration72 hours12.869.48 96 hours11.039.05 120 hours11.519.99Nutlin-3MDM2 inhibitor72 hours19.2415.81 96 hours16.8614.83 120 hours15.8114.00LY294002PI3K inhibitor72 hours4.3653.86 96 hours4.3122.73 120 hours4.8013.55ErlotinibEGF-R inhibitor72 hours2.73NA 96 hours2.562.29 120 hours2.662.34BI-2536PLK-1 inhibitor72 hours0.00590.35 96 hoursND0.11 120 hoursND0.12VX-680Aurora kinase inhibitor72 hours17.23ND 96 hours6.07ND 120 hours5.21ND 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 3672.