tbuckley/cabot-search huggingface dataset:
Abstract 322: Loss of Y chromosome in urological tumors
Authors: Sarah Minner, Adisa Kilgué, Phillip Stahl, Christoph Handel, Wolfgang Höppner, Walter Wagner, Roland Dahlem, Michael Rink, Christian Eichelberg, Thorsten Schlomm, Luigi Terracciano, Holger Moch, Margit Fisch, Ronald Simon, Guido Sauter
Journal: Cancer Research (2010)

Abstract Introduction and Objective Y chromosome losses have been associated with various malignant tumors including bladder cancer, kidney cancer and prostate cancer. Conflicting data exist on the potential prognostic role of Y chromosome losses in these urological malignancies and on whether Y losses could be age-related. The aim of this study was to further clarify the potential relevance of Y chromosome losses in these tumors with respect to tumor phenotype, clinical outcome and patient age. Methods Preexisting tissue microarrays (TMA) of bladder (573 tissue samples from male patients), kidney (447 tissue samples from male patients) and prostate cancer (3261 tissue samples) with long-term clinical follow-up data were used in this study. Y chromosome losses were analyzed by dual-labeling FISH (fluorescence in situ hybridization) using centromere Y and X probe. Results Y losses were seen in 22% of bladder cancers. There was no significant age difference between patients having tumors with (67.4 +/-2.1years) or without (67.3 +/-1.2 years) Y losses (p=0.6294). Y losses were unrelated to tumor grade (p=0.7831) and stage (p=0.6140). There was no correlation between Y losses and survival in 224 invasive urothelial cancers (pT2-4; p=0.2324). Y losses were not associated with an increased risk for recurrences in 197 analyzed pTa tumors (p=0.7649) or increased progression risk in 76 analyzed pT1 tumors (p=0.4582). In kidney cancer Y losses were seen in 23% of cases. Likewise, there was no significant age difference between patients having tumors with (59.2 +/-3.6 years) or without (61.2+/-1.5 years) Y losses (p=0.5873). Y losses were unrelated to tumor grade (p=0.3111) and tumor stage (p=0.2511). There was also no correlation between Y losses and survival (p=0.7431). Remarkably, Y losses were seen in only 13 of 2826 (0.5%) analyzable cases of prostate cancers. The number of Y chromosome losses was too low for further statistical analyses. Conclusions These data show, that Y losses are frequent in urinary bladder cancer and kidney cancer, but lack association with tumor phenotype, clinical outcome and patient age. While the mechanism for Y losses in these cancers remains unclear, our data do not suggest clinical significance. In contrast to bladder and kidney cancer, Y chromosome losses were almost absent in prostate cancer. This may suggest that prostate epithelial cells are highly dependent on proper function of at least one chromosome Y gene. 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 322.
Abstract 1480: The effect of Metformin on microtentacle formation and stabilization in breast cancer cells.
Authors: Kristi Chakrabarti, Rebecca A. Whipple, Amanda E. Boggs, Monica S. Charpentier, Jana Slovic, Michele I. Vitolo, Stuart S. Martin
Journal: Cancer Research (2013)

Abstract Metastasis is one of the main causes of mortality in women with breast cancer. Epithelial-to-mesenchymal transition (EMT) has emerged to be a key mediator of breast cancer metastasis. It has previously been shown that EMT can stabilize and increase microtentacles (McTNs) in breast cancer cell lines and enhance their metastatic potential. McTNs are dynamic, microtubule-enriched plasma membrane extensions that are stabilized with the exposure of a carboxy-terminal glutamic acid residue in alpha-tubulin (Glu-tubulin). McTN stabilization has been shown to promote tumor cell aggregation and reattachment in vitro. In this study, we investigated the effect of EMT suppression on McTN formation and stabilization in breast cancer cells by the dimethyl biguanide, Metformin. While it is widely used to treat type 2 diabetes, Metformin has more recently been shown to inhibit EMT in multiple breast cancer cell lines. We show here that Metformin decreased mesenchymal markers, such as N-cadherin and vimentin, in a dose-dependent manner in MDA-MB-231 breast cancer cells. Confocal and fluorescent microscopy was used to visualize and quantify McTN formation in these cells. There was a significant decrease in McTNs in MDA-MB-231 cells treated with 5mM Metformin for 24 hours. We correlated the decrease in the number of McTNs with a decrease in Glu-tubulin protein levels, which suggests that Metformin also inhibits McTN stabilization. The decrease in McTN formation and stabilization was also associated with diminished tumor cell reattachment in vitro. In addition, Metformin was able to protect MDA-MB-231 cells from increased McTN formation induced by the microtubule stabilizing agent, Taxol. Metformin's mechanism of action on breast cancer cells to elicit these cytoskeletal modifications has yet to be elucidated. However, these results suggest a role for Metformin at multiple stages of tumor progression to protect breast cancer patients from clinical spread of disease. Citation Format: Kristi Chakrabarti, Rebecca A. Whipple, Amanda E. Boggs, Monica S. Charpentier, Jana Slovic, Michele I. Vitolo, Stuart S. Martin. The effect of Metformin on microtentacle formation and stabilization in breast cancer cells. [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 1480. doi:10.1158/1538-7445.AM2013-1480
Online marketing of personalised cancer tests discusses benefits more than limitations, study shows
Authors: S. Mayor
Journal: BMJ (2015)

Internet sites marketing personalised cancer tests discuss the benefits more than the limitations of their products, and many promote tests that have not been validated, a study analysing the content of these websites has found.

Researchers analysed the information on 55 websites that marketed personalised cancer medicine, defined as “products or services that could be used to tailor, personalise, or individualise care based on …
AB0162 Shared decision making between patient and rheumatologist using a novel touch-panel system for treating rheumatoid arthritis to target
Authors: A. Kunii, N. Yokogawa, T. Oguma, K. Nakahara, N. Matsubara, M. Morimoto, K. Yokoyama, A. Warashina, E. Todoroki, K. Shimada, K. Kagawa, S. Ohshima, S. Sugii
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> "Treating to target (T2T) recommendations" are formulated to improve the management of rheumatoid arthritis (RA) in clinical practice. The following four overarching principles are highlighted: "(A) The treatment of rheumatoid arthritis must be based on a shared decision between patient and rheumatologist, (B) The primary goal of treating the patient with rheumatoid arthritis is to maximise long-term health-related quality of life through control of symptoms, prevention of structural damage, normalisation of function and social participation, (C) Abrogation of inflammation is the most important way to achieve these goals, (D) Treatment to target by measuring disease activity and adjusting therapy accordingly optimises outcomes in rheumatoid arthritis." However, the T2T recommendations do not specify concrete and effective methods to implement. <h3>Objectives</h3> We developed an original computerized touch-panel system for facilitating the assessment of RA, called MiRAi.[1] We upgraded MiRAi to allow patients to track their RAPID3 score independently on their monitor even before consulting their physician. We evaluated whether this novel touch-panel system promoted shared decision making between patient and rheumatologist. <h3>Methods</h3> After obtaining the informed consent, registered nurses asked RA patients to fill out the same questionnaires before, and 6 months after, introduction of the touch-panel system. The questionnaires were anonymous and the physicians were blinded. The questionnaire included six visual analog scales (VAS): agreement to each of the four overarching principles, degree of "shared decision-making", and degree of satisfaction with the care received. Since the key concept of the T2T is summarized in principle "D" as outlined above, we classified subjects with the lower quartile VAS of "D" (before introduction of this system) in the "poor comprehension group" and the rest in the "fair/good comprehension group". We then compared the VAS between these two groups. <h3>Results</h3> The IRB approved this project. The initial evaluation was obtained from 302 patients. Six months after this system was introduced, the second evaluation was collected from 261 patients (86.4%). Whereas the "Poor comprehension group" showed improvement in all VAS except the RAPID3 score, the "fair/good comprehension group" showed improvement in RAPID3 and as well as satisfaction with the medical care they received. <h3>Conclusions</h3> The novel touch-panel system may promote comprehension and implementation of T2T recommendations. <h3>References</h3> Kagawa K, et al. Usefulness of touch-panel method for the evaluation of functional ability in rheumatoid arthritis. Ann Rheum Dis 2012;71(Suppl 3):742 <h3>Disclosure of Interest</h3> None Declared
Gastric Duplication cyst
Authors: JASON R. DITTRICH, STEPHANIE E. SPOTTSWOOD, PAUL R. JOLLES
Journal: Clinical Nuclear Medicine (1997)

Gastric duplication cysts are uncommon congenital anomalies, and examples imaged with scintigraphy are rarely reported in the literature. The authors report an infant with duplication of the stomach, which was extensively evaluated using scintigraphy, ultrasound, computed tomography, and upper gastrointestinal series. The role of multimodality imaging is discussed, and correlative surgical and histologic findings are presented.
P2-08-07: Ex-Vivo High Resolution MRI of Sentinel Lymph Nodes Following Subcutaneous Injection of Superparamagnetic Iron Oxide Nanoparticles.
Authors: M Douek, Beek O ter, L Johnson, Q Pankhurst, J Parikh, T Schaeffter, A Purushotham, G Charles-Eduards
Journal: Cancer Research (2011)

Abstract Background: Superparamagnetic iron oxide (SPIO) enhanced axillary MRI is a promising novel imaging modality that could be used to characterize sentinel nodes non-invasively. In order to better characterize lymph nodes and evaluate their morphological features, we imaged nodes ex-vivo using high resolution MRI, following a pre-operative subcutaneous injection of SPIO. Material and methods: Prior to surgery patients received a circumareolar injection of SPIO (Endorem, Guerbet, Paris) into the upper outer quadrant of the affected breast. Sentinel lymph nodes excised during surgery were transported to the imaging department fresh. Nodes were placed in glass tubes and scanned using a Bruker 9.4T MRI system (T2 mapping: turbo spin echo, 16 equi-spaced TEs from 7.1 to 113.6 ms, TR = 1616 ms. T2* mapping: gradient echo, 6 equi-spaced TEs from 3.5 to 21 ms, TR = 1000 ms, flip angle = 30 degrees. Diffusion-weighted: spin echo, b-values 0 and 1000 s/mm2, TE = 18 ms, TR = 6500 ms.). Slice thickness was 1 mm with an in plane spatial resolution of 100μm. Image analysis was undertaken using Osirix (v3.8, 64-bit). Results: A total of 40 nodes were successfully imaged, excised from 14 patients. The internal architecture of nodes was clearly seen and in the 3 involved nodes, a macrometastasis was identified. Three patients received a 4ml injection of SPIO and 11 patients, a 2ml injection. More SPIO deposition was seen within nodal sinuses following 4ml of SPIO, but there was no significant decrease in mean T2 value. Four nodes were re-imaged following formalin fixation and nodal architecture was unchanged with a trend towards an increase in mean T2 values within nodes. SPIO was identified in all sentinel nodes. Discussion: Ex-vivo MRI with subcutaneous SPIO contrast, is a useful method for imaging and characterization of sentinel nodes. A better understanding of ex-vivo features is a useful aide to understanding the morphological features seen following in-vivo SPIO enhanced axillary MRI. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-07.
Alcohol Consumption and Mortality among Middle-Aged and Elderly U.S. Adults
Authors: Michael J. Thun, Richard Peto, Alan D. Lopez, Jane H. Monaco, S. Jane Henley, Clark W. Heath, Richard Doll
Journal: New England Journal of Medicine (1997)

Alcohol consumption has both adverse and beneficial effects on survival. We examined the balance of these in a large prospective study of mortality among U.S. adults.Of 490,000 men and women (mean age, 56 years; range, 30 to 104) who reported their alcohol and tobacco use in 1982, 46,000 died during nine years of follow-up. We compared cause-specific and rates of death from all causes across categories of base-line alcohol consumption, adjusting for other risk factors, and related drinking and smoking habits to the cumulative probability of dying between the ages of 35 and 69 years.Causes of death associated with drinking were cirrhosis and alcoholism; cancers of the mouth, esophagus, pharynx, larynx, and liver combined; breast cancer in women; and injuries and other external causes in men. The mortality from breast cancer was 30 percent higher among women reporting at least one drink daily than among nondrinkers (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.6). The rates of death from all cardiovascular diseases were 30 to 40 percent lower among men (relative risk, 0.7; 95 percent confidence interval, 0.7 to 0.8) and women (relative risk, 0.6; 95 percent confidence interval, 0.6 to 0.7) reporting at least one drink daily than among nondrinkers, with little relation to the level of consumption. The overall death rates were lowest among men and women reporting about one drink daily. Mortality from all causes increased with heavier drinking, particularly among adults under age 60 with lower risk of cardiovascular disease. Alcohol consumption was associated with a small reduction in the overall risk of death in middle age (ages 35 to 69), whereas smoking approximately doubled this risk.In this middle-aged and elderly population, moderate alcohol consumption slightly reduced overall mortality. The benefit depended in part on age and background cardiovascular risk and was far smaller than the large increase in risk produced by tobacco.
Assessment of Quality-of-Life Outcomes
Authors: Marcia A. Testa, Donald C. Simonson
Journal: New England Journal of Medicine (1996)

Since 1948, when the World Health Organization defined health as being not only the absence of disease and infirmity but also the presence of physical, mental, and social well-being,1 quality-of-life issues have become steadily more important in health care practice and research. There has been a nearly exponential increase in the use of quality-of-life evaluation as a technique of clinical research since 1973, when only 5 articles listed “quality of life” as a reference key word in the MEDLINE data base; during the subsequent five-year periods, there were 195, 273, 490, and 1252 such articles. The growing fields of outcomes . . .
FRI0293 Rheumatoid arthritis and spondyloarthropathies in clinical remission have the same rates of flare in pregnancy, more elevated if therapy before conception was a biologic agent
Authors: S. Giacuzzo, M. Padovan, G. Castellino, R. Capucci, M. Govoni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The activity of the rheumatic diseases can be influenced by pregnancy and puerperium. Improvement of rheumatoid arthritis (RA) and psoriatic arthritis (PA) was described in retrospective studies in about 75% of pregnant patients, whereas in ankylosing spondylitis (AS) there is no relevant change in disease activity. Most of these data come from study in which were enrolled patients with moderate-hight disease activity at pregnancy onset. <h3>Objectives</h3> to assess rate of disease flare in patients with RA and spondyloarthropathies (SpA) in clinical remission during and after pregnancy <h3>Methods</h3> We included 18 patients with RA (19 pregnancies), 12 with undifferentiated spondyloarthropathies (14 pregnancies), 4 with psoriatic arthritis and 2 with ankylosing spondylitis (AS) in clinical remission (DAS28-PCR-3v &lt;2.6; BASDAI &lt;4, no extra-articular manifestations) at last visit before pregnancy. Twelve patients were exposed to anti-TNF agents (5 with RA and 7 with SpA) wich were stopped when pregnancy started and 1 patient with RA had completed the last cycle with Rituximab 3 months beforeconception. Clinical examination was performed monthly during pregnancy and 12 weeks post-delivery. Assessment of RA and SpA with peripheral arthritis was performed by DAS28-CRP with 3 variables (DAS28-CRP-3v) and assessment of AS by the BASDAI. Disease flare was defined as increase in DAS28&gt;1.2, BASDAI &gt;4 or new/worsened extra-articular manifestations requiring therapy. <h3>Results</h3> Disease relapses in RA and SpA were observed respectively in 26% and 15% in first trimester, 42% and 15% in second trimester, 21% and 30% in third trimester, 61% and 55% in puerperium. Clinical remission was persistently maintained during gestation in 53% of RA patients and 50% of SpA patients. Although we found a trend of high rate of relapses during the second trimester in patients with RA it was not statistically significant. It is worth noting that the highest rates of flares occurred in patients previously exposed to biotechnology drugs, regardless of the underlying disease (100% vs 50%; p 0.0018). <h3>Conclusions</h3> Disease relapse occurred with similar rates in RA and SpA patients during pregnancy and puerperium. The rates of relapse were higher in patient previously treated with biologic agents, probably because of greater severity of underlying disease. Data coming from this preliminary analysis demonstrated that rheumatic diseases in clinical remission reached after biologic treatment may be at risk of relapse when these drugs are withdrawn in early pregnancy. <h3>Disclosure of Interest</h3> None Declared
Abstract 5556: Discovery of RKI-18, a small molecule that inhibits Rho kinases 1 and 2, migration and invasion of human tumors.
Authors: Ronil A. Patel, Yan Lui, Binglin Wang, Ronshi Li, Said M. Sebti
Journal: Cancer Research (2013)

Abstract Signal transduction pathways that are mediated by ROCK1 and ROCK2 trigger cell migration, invasion and metastasis. This prompted us to design and synthesize novel Rho-kinase inhibitors (RKIs). Here, we show that one of our most potent RKIs, RKI-18 (IC50 397 nM (ROCK1) and 349 nM (ROCK2)) but not its inactive closely related analogue RKI-11 suppresses potently the phosphorylation of the ROCK substrate MLC2 in intact human cancer cells. Furthermore, RKI-18 is highly selective at inhibiting P-MLC2 over P-Akt, P-S6 and P-Erk ½ levels. RKI-18 suppresses ROCK-mediated actin fiber formation following stimulation with LPA as well as PAK-mediated lamelipodia and filopodia formation following bradykinin or PDGF stimulation. Furthermore, RKI-18 but not RKI-11 inhibits migration, invasion and anchorage-independent growth of human breast cancer cells. The fact that RKI-18, the active ROCK inhibitor, but not RKI-11, its inactive analogue, is effective at suppressing malignant transformation suggests that preventing migration, invasion and anchorage-independent growth with RKI-18 is likely due to inhibition of ROCK. Further advanced preclinical studies are required to determine the potential of RKI-18 as an anti-metastatic agent. Citation Format: Ronil A. Patel, Yan Lui, Binglin Wang, Ronshi Li, Said M. Sebti. Discovery of RKI-18, a small molecule that inhibits Rho kinases 1 and 2, migration and invasion of human tumors. [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 5556. doi:10.1158/1538-7445.AM2013-5556
Can Age-Associated Memory Decline Be Treated?
Authors: Mark D'Esposito, Adam Gazzaley
Journal: New England Journal of Medicine (2011)

Many older adults believe that their memory is not as good as it was when they were younger. An epidemiologic study in Finland documented that 76% of persons over the age of 60 years reported problems with their memory.1 Age-associated memory decline has been well studied and refers to changes in the aging brain that affect cognition but have no clear pathologic explanation. Because of the rapid increase in the number of older people in the world's population, the development of treatments for age-associated memory decline must be a high public health priority. Yet no effective, validated treatments currently exist. . . .
Abstract 4874: Small molecule inhibitor of ezrin inhibits metastasis in a transgenic mouse model of osteosarcoma
Authors: Jared T. Murdoch, Sung-Hyeok Hong, Gulay Bulut, George W. Kosturko, Lauren E. Drebing, Jeffrey A. Toretsky, Aykut Uren
Journal: Cancer Research (2012)

Abstract Osteosarcoma is the predominant primary bone cancer in children with a low survival rate due to pulmonary metastasis. Research on the molecular mechanism driving pulmonary metastasis implicates the cytoskeletal protein ezrin as the critical component of the disease pathology. Ezrin links the actin cytoskeleton to the plasma membrane proteins, and its overexpression is associated with poor survival in patients and increased invasion in osteosarcoma cell lines. We used surface plasmon resonance technology to screen small molecule libraries for compounds directly binding to ezrin. Two molecules, NSC305787 and NSC668394, were chosen based on their ezrin binding affinities and ability to inhibit ezrin in multiple functional, biochemical, cellular, and in vivo assays. To test the anti-metastatic activity of these molecules in vivo, we utilized a tissue-specific transgenic mouse model expressing Cre recombinase to excise the Retinoblastoma (Rb) and p53 tumor suppressor genes in osteoblast progenitor cells. These animals develop spontaneous osteosarcoma with 100% penetrance and high frequency of liver and lung metastases, mimicking human disease. We tested the anti-metastatic potential of ezrin inhibitors that we discovered, NSC305787 and NSC668394, in this clinically relevant mouse model. We started the treatment on one group of animals at 2 months of age before any detectable tumor is present and on a second group of animals only after detection of smallest palpable tumor. Animals in each group were randomly assigned to one of three treatment options: DMSO (Control), NSC305787, or NSC668394. Animals were observed for primary tumor growth and metastasis formation. All animals were euthanized when primary tumor volume reached 2.0cm3, when animals had severe cachexia, or when animals showed signs of pulmonary insufficiency. Mice treated with NSC305787 and NSC668394 did not show any changes in the growth of their primary tumors and experienced similar survival times. However, our results suggest that NSC305787 inhibits osteosarcoma metastasis to lungs as confirmed by histopathological analysis. Therefore, when combined with adjuvant chemotherapy and surgical resection of the primary tumor, targeting ezrin with small molecules may yield a positive outcome and greater survival in a clinical setting. 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 4874. doi:1538-7445.AM2012-4874