tbuckley/cabot-search huggingface dataset:
Abstract 2837: Diverse associations between <i>ESR1</i> polymorphisms and breast cancer development and progression
Authors: Shian-Ling DING, Jyh-Cherng Yu, Shou-Tung Chen, Shou-Tung Chen, Giu-Cheng Hsu, Pei-Ei Wu, Chen-Yang Shen
Journal: Cancer Research (2010)

Abstract Purpose: To test the hypothesis that polymorphisms of ESR1, encoding estrogen receptor α (ERα), are associated with susceptibility, clinical phenotype, and progression of breast cancer. Patients and Methods: A case-control study was performed on 940 patients with incident breast cancer and 1547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNPs) tagging all major polymorphisms of this gene were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility, and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression. Results. Three SNPs, located in one cluster in intron 1, were found to be important and the variant alleles showed a significant association with a decreased breast cancer risk and, coincidently, with low ERα expression in tumors. The tumorigenic contribution of these intron-1 SNPs was more obvious in combination with reproductive risk factors (p for interaction&amp;lt;0.05). Interestingly, the same SNPs showed a significant correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the five-year survival rate of all patients, but had opposite effects in ERα-negative and ERα-positive early-stage patients. Conclusions: Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERα in these two populations. 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 2837.
Case 31-2007
Authors: Hamid Rabb, Robert B. Colvin
Journal: New England Journal of Medicine (2007)

A 41-year-old man was admitted to the hospital because of abdominal pain, nausea, and an elevated serum creatinine level. Six days earlier, he had had chills and malaise and had taken ibuprofen. Symptoms persisted, and weakness, abdominal pain, nausea, and anorexia developed. He went to an emergency room, where elevated serum creatinine and urea nitrogen levels were noted. The urinary sediment contained granular casts.
A review of the Inuit oncology patients treated at the Ottawa Hospital Cancer Centre.
Authors: Michela Febbraro, Johanna Spaans, Gonzalo G Alvarez, Timothy R. Asmis
Journal: Journal of Clinical Oncology (2013)

e17563 Background: Cancer is a major health concern among Canada’s northern Inuit population. Limited Inuit specific data exists on the geographical isolation and the effect on treatment outcomes of Inuit referred to urban hospitals for cancer treatment. Methods: A retrospective chart review of all Inuit referred to the Ottawa Hospital Cancer Centre from Nunavut, Canada (distance: 1298 miles) between 2001-2011 was conducted. Demographic, diagnostic and treatment related information was collected on all patients, including the number of visits made by each Inuit patient from Nunavut to OHCC for treatment. Results: 234 Inuit (male: 74, female: 160) were referred to OHCC with a diagnosis of cancer. Mean age at diagnosis was 58.5 years (sd 14.61). Over half the patients were current smokers (54%) and 39% of patients had a history of tuberculosis (TB). Among Inuit men, lung (n=32, 43%), colorectal (n=11, 14%) and nasopharyngeal (n=9, 12%) cancer were the most common diagnosis. Among Inuit women, the most common cancers were lung (n=72, 45%), colorectal (n=32, 20%), breast (n=21, 13%), cervical (n=11, 7%) and nasopharyngeal (n=7, 4%). Metastatic disease at presentation was common (n=76, 38%). Primary cancer was amenable to surgery in n=57 patients. An equivalent number of patients (n=82) received adjuvant/definitive radiation therapy (RXT) and adjuvant chemotherapy, with n=52 receiving chemoradiation. Palliative RXT and chemotherapy was received by 64 and 51 patients, respectively. Among patients receiving chemotherapy, there were no cases of TB reactivation and no treatment related serious adverse outcomes or deaths. Average number of trips made to Ottawa for treatment was n=7 (sd 7.90) with the upper quartile averaging n=10 trips. Conclusions: Lung, colorectal and nasopharyngeal cancers are over-represented among Canadian Inuit, who often present with advanced disease. Travel burden is significant among patients receiving treatment. Improved cancer screening and oral molecularly targeted therapies that can be delivered in remote northern communities are likely to improve the experience and treatment outcomes among Canadian Inuit.
Abstract 4006: Biochemical characteristics of functional domain of KITENIN: Its implication in AP-1 signal activation and colorectal cancer cell motility
Authors: Jeong A Bae, Eun Gene Sun, So Yeon Park, Hangun Kim, Kyung Keun Kim
Journal: Cancer Research (2012)

Abstract Background &amp; aims: KITENIN (KAI1 C-terminal interacting tetraspanin) is not only a membrane-associated protein but also a functional protein promoting the invasiveness of colorectal cancer (CRC) cells. Recent studies about the mechanism of KITENIN function in the CRC cells indicate that KITENIN plays a pivotal role in tumor initiation and promotion through activating the activator protein-1 (AP-1) signaling. However, the contribution of each functional domain of KITENIN to AP-1 signaling is still unknown and the biochemical properties of C-terminal region of KITENIN were investigated. Methods: To compare the biochemical and functional properties of KITENIN deletion mutants with wild-type KITENIN, the various mutant constructs of C-terminal region (238-512 aa) were generated and being expressed in the 293T and Caco2 cells. AP-1 activity was measured via AP-1 luciferase reporter assays, and the cellular phenotypes of these cells expressing KITENIN mutants were examined via in vitro cell invasion and wound-healing assays. Results: KITENIN mutant with deletion of C-terminal 63 amino acids (DCKIT) markedly increased the AP-1 activity in contrast to other deletion mutants and wild-type KITENIN. Also, DCKIT increased the degradation of Dvl2 and stability of c-Jun, which are responsible for AP-1 activation by KITENIN. The C-terminal fragment of KITENIN (KICD, roughly 30 kDa) was generated and preferentially translocated to the nucleus after PMA treatment, but its functional significance is under investigation. A mutant construct of 408ALRA411-KITENIN was obtained by mutation of YXXΨ motifs, which directs the clathrin-dependent endocytosis of membrane-spanning proteins. This mutation did not influence the AP-1 activity, cell invasiveness, and cell migration by KITENIN but disrupted the interaction of KITENIN with Dvl2. Moreover, co-expression of this mutant with ErbB4 exhibited more attenuated AP-1 activity than that of forced expression of wild-type KITENIN and ErbB4. These results indicate that endocytosis of KITENIN and subsequent interaction with Dvl2 is essential to activating AP-1 signal and modulating cell motility by KITENIN. Conclusion: These biochemical properties of deletion mutants of KITENIN suggest that the C-terminal region of KITENIN is an important component for modulating AP-1 signal and CRC cell motility by KITENIN. 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 4006. doi:1538-7445.AM2012-4006
P361MIP1 causes cardiomyopathy
Authors: B Buyandelger, C Mansfield, S Kostin, O Choi, RL Isaacson, G Knoell, SJ Mcsweeney, E Lara-Pezzi, H Milting, R Knoell
Journal: Cardiovascular Research (2014)

Purposes: Mutations in sarcomeric proteins are a major cause of hereditary cardiomyopathies. Muscle LIM protein (MLP, CSRP3) is involved in cardiac mechanosensation and important for myocyte-specific survival pathways. Identification of novel MLP interacting proteins (MIP) may provide novel insights into underlying molecular mechanisms of human disease.
FRI0432 Well-being, sleep and coping had good psychometric properties in rheumatoid arthritis (RA): A subanalysis of an etanercept trial:
Authors: L. Gossec, Y. Brault, I. Logeart, M. Dougados
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In RA, there is increasing interest in "unusual" patient-reported outcomes (PROs), over and above pain, function and fatigue; namely, quality of sleep, well-being and ability to cope [1]. Although these outcomes are important from the patient's point of view, are they useful as outcome measures and in particular, are they reliable, and responsive, i.e., do they improve when disease improves with treatment? <h3>Objectives</h3> To assess the reliability and responsiveness after introduction of etanercept, of different PROs. <h3>Methods</h3> <i>Study:</i> open-label 12-week trial of etanercept in RA [2]. <i>PROs of interest:</i> numeric rating scales (NRS) for sleep, physical and emotional well-being, and coping [3]. <i>Comparison outcomes:</i> "standard" PROs, namely, pain NRS, patient global assessment of disease activity (PGA), modified-HAQ (mHAQ) and fatigue NRS. <i>Reliability:</i> assessed between screening and baseline visits by intra-class correlation (ICC). <i>Responsiveness:</i> assessed between baseline and 12 weeks, by standardized response means (SRM). Only patients with at least 1 etanercept injection were analysed. <h3>Results</h3> In all, 108 of the 120 screened patients received at least one etanercept injection: mean age, 54 (SD 13) yrs, mean disease duration 8 (SD 7), 75% were women, all were biologic naïve. Disease was active: mean DAS28 5.5 (SD 0.8), mean mHAQ 0.9 (SD 0.5), mean PGA, 6.5 (SD 1.9). At 12 weeks, mean DAS28 was 3.4 (SD 1.2). Reliability was highest for sleep, and lowest for PGA and pain, whereas responsiveness was highest for pain and PGA, and lowest for mHAQ (Table). <h3>Conclusions</h3> NRS assessing sleep, well-being and coping were found to be generally as reliable and as responsive as "usual" PROs in RA. mHAQ showed poor responsiveness possibly due to floor effects. Sleep and coping were the least responsive "unusual" PROs in this trial, indicating these domains of health may be less accessible to biologic treatment. When assessing the patient's perspective on treatment, it is feasible and valid to measure "unusual" domains of health by NRS. <h3>References</h3> Kirwan JR et al, J Rheumatol. 2011;38(8):1711-5. Dougados M et al, J Rheumatol. 2011;38(11):2326-8. Gossec L et al, Ann Rheum Dis 2011;70(6):935-42. <h3>Disclosure of Interest</h3> L. Gossec Consultant for: Abbott, BMS, Pfizer, Roche, UCB, Y. Brault Employee of: Pfizer, I. Logeart Employee of: Pfizer, M. Dougados Consultant for: Abbott, BMS, Pfizer, Roche, UCB,
Clonally unrelated BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronic myeloid leukemia
Authors: R Manley, J Cochrane, M McDonald, S Rigby, A Moore, A Kirk, S Clarke, PE Crossen, CM Morris, WN Patton
Journal: Leukemia (1999)
ELECTROCARDIOGRAPHIC CHARACTERISTICS ASSOCIATED WITH IN-HOSPITAL OUTCOME IN PATIENTS WITH LEFT MAIN ACUTE CORONARY SYNDROME
Authors: Tomonori Itoh, Takayuki Iida, Fumito Tanimura, Kyoko Takahashi, Hideki Nakamura, Satoshi Nakajima, Motoyuki Nakamura, Yoshihiro Morino
Journal: Journal of the American College of Cardiology (2016)
Effect of Mopidamol on Survival in Carcinoma of the Lung and Colon: Final Report of Veterans Administration Cooperative Study No. 188
Authors: L. R. Zacharski, T. E. Moritz, L. A. Baczek, F. R. Rickles, R. L. Edwards, W. B. Forman, R. J. Forcier, C. J. Cornell, C. M. Haakenson, H. S. Ballard, E. D. Crum, G. J. Johnson, J. Levine, W. K. Hong, J. F. O'Donnell, R. L. Schilsky, Q. S. Ringenberg, F. Robert, M. B. Spaulding, K. Tornyos, C. Williams, S. Zucker, C. S. Faulkner, W. L. Eaton, C. L. Hoppel
Journal: JNCI Journal of the National Cancer Institute (1988)

Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration. RA-233 was not toxic. The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested, no differences in survival were observed. These results suggest that RA-233 is useful in the treatment of N-SCLC of limited extent. They also suggest that therapeutic intervention aimed at modified intracellular pathways might constitute a novel investigative approach to the treatment of cancer.
AB1102 Giving Infliximab Infusions at Home: A Pilot Study: Table 1
Authors: S. Shaffu, A. Kinder
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The use of Infliximab in inflammatory arthritides (IAs) has been extensive with statistically favourable responses in disease activity. Despite proven clinical improvement, biological agents such as Infliximab are costly. Infliximab is given as an intravenous infusion on a monthly basis. To date these infusions have been performed in secondary care. At present, a home infusion service as part of Healthcare at Home is funded by MSD. This service was extended to the Leicestershire region, as part of a pilot study. <h3>Objectives</h3> The aim of this study was to improve cost effectivity of Rheumatological services within Leicestershire, an important exercise at a time of financial crisis within the NHS. <h3>Methods</h3> Ten patients with IAs such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) were identified as receiving Infliximab through the University Hospitals of Leicester Rheumatology biologics database and invited to participate in this pilot study. The nurse administered the Infliximab within the patients9 own homes. Length of infusions and visits were analysed and number of vials used recorded. A service satisfaction questionnaire was distributed to each patient. <h3>Results</h3> All patient participants were established on Infliximab having had over 8 infusions each. One patient had PsA, 3 had AS and 6 had RA. The median age was 64 years. A total of 42 infusions were administered, 39 of which were given at home and 3 were given in hospital. Thirty of the infusions were successful, yet 12 infusions were not commented upon. There were no adverse reactions and only 1 case incurred wastage due to apparatus issues. Infusions lasted up to 1 hour and longest total visit time was 3 hours and 15 minutes. Cost savings of £5,066.34 per infusion of 10 patients and £32,931.21 per annum were made (Table 1). Patient satisfaction was analysed via a questionnaire. Of the 9 responses received, the general feedback was that this was a great development and preferred to the hospital setting. <h3>Conclusions</h3> Providing Infliximab within patients9 homes has proven that an immense cost saving can be made on annual basis thus allowing the funding of other services essential to delivering optimal care to our Rheumatology patients. Furthermore, this service is an attractive option as it abides with NHS policy, providing care closer to home and giving patients greater choice as to how and where they receive their care. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4120
RARE-10SYLVIAN FISSURE DERMOID CYST WITH GIANT CELL REACTIVITY: A REPORT OF A RARE CASE AND REVIEW OF THE LITERATURE
Authors: Juanita Garces, Mansour Mathkour, Bryce Beard, Marcus Ware
Journal: Neuro-Oncology (2015)

INTRODUCTION: Dermoid cysts are rare intracranial tumors that are most commonly found infratentorially and along the midline. These benign lesions, which are the result of defective closure of neuroectodermal folds containing mesenchymal elements, are usually discovered in late childhood or early adulthood. Characterized by slow growth and often found incidentally, these lesions can nonetheless have severe complications, notably rupture leading to chemical meningitis. They infrequently present as a supratentorial and lateralized mass. As such, Sylvian fissure dermoid cysts are exquisitely rare. To the best of our knowledge, there are 11 prior reported cases of Sylvian fissure dermoid cysts. We present a rare case of a dermoid cyst with giant cell reactivity suggestive of focal rupture and chronic inflammation. CASE: A 61 year-old female who presented with new onset seizures was seen at our institution. On physical examination she was neurologically intact. Magnetic resonance imaging revealed a right insular mass measuring 4.3x4.5cm with compression of the ipsilateral frontal and temporal lobe. The mass was non-enhancing; however it was bright on diffusion-weighted imaging, suggesting a dermoid cyst. She underwent craniotomy for tumor resection. Histological analysis revealed keratinizing squamous epithelium, rare sebaceous glands and hair follicles consisted with dermoid cyst. There was also an associated giant cell reaction involving the fibrous capsule of the cyst. At 18-months post-operative, she is seizure free and without evidence of recurrence. CONCLUSION: The dermoid cyst in our patient was not grossly ruptured, however histopathological analysis revealed giant cell reactivity indicating focal rupture. The relationship between rupture of dermoid cysts and inflammation is not well elucidated. It is not known whether symptoms occur immediately after rupture or as an acute manifestation of a chronic process following rupture. As these lesions and their rupture are quite rare, more diligence regarding details of histopathology for dermoid cysts is needed.
Abstract 602: Silencing of the androgen receptor (AR) with a novel mRNA antisense oligonucleotide causes antitumor effects in xenograft models of prostate cancer
Authors: Yixian Zhang, Stephen Castaneda, Steven Kim, Patricia Kraft, Raj Bandaru, David Filpula, Lee M. Greenberger, Ivan D. Horak
Journal: Cancer Research (2010)

Abstract Background: The AR is a ligand-activated transcriptional factor that plays an important role in prostate cancer. While androgen-deprivation therapies typically inhibit tumor growth, tumor recurrence due to the castration resistant form of the disease frequently occurs and leads to mortality. Nevertheless, castration-resistant tumors are still dependent on a functional (AR). Therefore, inhibition of AR expression, rather than systemic androgen deprivation, may provide a novel strategy for treatment of advanced prostate cancer. We have developed a novel locked nucleic acid (LNA)-based antisense oligonucleotide (ON), EZN-4176, which down-modulated AR and inhibited tumor growth. Methods: The target mRNA down-modulation, growth inhibition, luciferase activity, protein inhibition, and reduction of prostate specific antigen (PSA; an AR downstream target and biomarker of prostate cancer) were evaluated by qRT-PCR, MTS, SteadyGlo, western blot analysis, and ELISA assay, respectively, in LNCaP cancer cell lines. A mismatched LNA antisense oligo (EZN-4176MM) and an AR negative cell line (PC-3 prostate cancer) served as controls. Additionally, the effect of EZN-4176 on DHT-induced AR transcriptional activity was evaluated in LNCaP cells containing an AR-responsive luciferase reporter. In vivo, therapeutic efficacy of EZN-4176 was evaluated in the AR-positive CWR22 (androgen dependent). Results: In vitro, in the absence of any transfection reagent, EZN-4176 but not the mismatched control (EZN-4176MM) inhibited the growth of DHT-induced LNCaP cells. The growth reduction correlated with AR down-modulation and its down-stream target gene expression and AR-responsive luciferase activity. In vivo, EZN-4176, prepared in the absence of a delivery vehicle, demonstrated dose-dependent inhibition of mRNA of AR, PSA, and TMPRSS2 as well as protein level of AR in androgen-sensitive CWR22 tumor xenografts, resulting in significant tumor growth inhibition (TGI) (∼55%) (similar to high-dose Casodex® [bicalutamide] treatment). Cy5.5-labeled EZN-4176 was shown to localize in subcutaneous CWR22 or LNCaP tumor xenografts using xenogen imaging system. In castration-resistant tumor cells, EZN-4176 potently and specifically inhibited the growth of C4-2b cells as well as down-regulated AR-luciferase reporter systems. More importantly, AR and PSA mRNA were inhibited in both castration-resistant C4-2b and 22RV1 tumor xenografts. Conclusions: Our data suggest that AR mRNA down modulation by EZN-4176 inhibits prostate tumor growth and provides a novel strategy to treat advanced prostate cancer. 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 602.
Abstract 2101: <i>GBM: miR-34a</i> acts as a tumor suppressor and prognosis maker as well as modulating EGFR
Authors: Dong Yin, Seishi Ogawa, Norihiko Kawamata, Nils H. Thoennissen, Weikai Chen, Amanda Leiter, Michelle Ham, Ngan B B. Doan, Jonathan W. Said, Keith L. Black, H. Phillip Koeffler
Journal: Cancer Research (2010)

Abstract The whole genomic gene copy number was measured using single nucleotide polymorphism DNA microarray (SNP-Chip). Chromosome 1p36.23 was frequently deleted (19 of 55 clinical samples, 35 %) and EGFR was often amplified (35 of 55, clinical samples 66 %) in glioblastoma multiform (GBM). microRNA 34a (miR-34a) localizes in this minimum common deleted 1p36.23 region. We hypothesized that miR-34a may act as a tumor suppressor in the brain. Interestingly, we found that the mean survival time was significantly shorten (p &amp;lt; 0.05) in the patients whose GBM showed both EGFR amplification and miR-34a deletion compared to those with either EGFR amplification, miR-34a deletion or normal levels of EGFR and miR-34a. Expression of miR-34a was significantly lower in GBM samples compared to normal brain tissue as examined using real-time RT PCR. Forced expression of miR-34a in GBM cell lines decreased their cell growth both in liquid culture and in immunodeficient mice; and the latter was associated with decreased angiogenesis. These cells also had decreased ability to migrate as detected by Boyden chamber and had profoundly low levels of cell cycle proteins (Cyclin -A1, -D1, -D3 and -B1, CDK2, as well as, E2F1, −3, and −4) and increased expression of cyclin kinase inhibitor (CKI) proteins, p21 and p27. Furthermore, the protein expression of EGFR was decreased in the cells with overexpression of miR-34a. Taken together, GBMs often acquire a miR-34a deletion and have low expression of this microRNA. The miR-34a probably normally acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell cycle proteins and EGFR. Individuals whose GBM have both deletion of miR-34a and amplification of EGFR have a particularly poor prognosis. 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 2101.