tbuckley/cabot-search huggingface dataset:
Abstract A21: MAGE cancer-testis antigens facilitate the degradation of p53 by E3 RING ubiquitin ligases
Authors: Patrick Ryan Potts
Journal: Cancer Research (2009)

Abstract Cancer testis antigens are aberrantly expressed in cancer cells but absent from normal somatic cells, and as such they constitute excellent targets for cancer immunotherapy. Surprising recent evidence suggests that their aberrant expression in cancer cells is not simply an inert consequence of widespread genomic deregulation, but rather an important functional event promoting the cancer phenotype. However, the mechanism through which these proteins promote cancer remains completely unknown due to the lack of structural or functional characterization. Here we report the structural and functional identity of the MAGE proteins, a large family of cancer testis antigens and ubiquitous proteins of previously unknown function. Through structural prediction, X-ray crystallography, and biochemistry we show that a conserved feature of the MAGE family of proteins is their ability to bind to E3 RING ubiquitin ligases, such TRIM28/KAP1. Surprisingly, MAGE-RING ubiquitin ligases share structural and biochemical similarities to Cullin-RING ubiquitin ligases. Most notably, MAGEs activate the ubiquitin ligase activity of E3 RING ubiquitin ligases. Furthermore, we show that the tumor suppressor p53 is a critical and direct target of MAGE-mediated ubiquitination and degradation in breast cancer. Thus we have identified a novel, cancer-specific regulator of p53 degradation and breast cancer survival and discovered the function of the enigmatic MAGE family of cancer testis antigens. These results underscore the importance of MAGE proteins as therapeutic targets for cancer. Citation Information: Cancer Res 2009;69(23 Suppl):A21.
Abstract 1221: Apoptosis is regulated by MCPH1 via p38 MAPK
Authors: Yong Hwa Jo, Yongung Eun Choi, Hyun Mi Park, Kyung-sik Yoon
Journal: Cancer Research (2010)

Abstract Microcephalin (MCPH1) is a member of the BRCA1 COOH terminal (BRCT) domain family of protein that involved in the cellular response to DNA damage. MCPH1 gene are associated with primary microcephaly (OMIM 251200), premature chromosome condensation, homologous DNA repair, chromosomal integrity, cell cycle arrest, telomerase activity and apoptosis. Recently reports, And MCPH1 is regulated the p53 phosphorylation in apoptosis, and enhanced E2F1-dependent apoptosis and the role of MCPH1 in p73 induction during DNA damage. And E2F1 activation leads to a transient increase in phosphorylation of the MAPK p38 and also leads to phosphorylation of p53 in apoptosis. But it is not unclear mechanisms that MCPH1/ E2F1 binging induced phosphorylation of p38 MAPK. We have used western blotting and immunopresipitation for detecting protein expression and also real-time PCR for RNA expression. Cell lines were used MCF7, MDA-MB231, MCF10A and U2OS. We use the anti-cancer drugs, as cisplatin and doxorubicin for induced the apoptosis. Anti-cancer drugs are induced the MCPH1 protein expression for 2h∼6h, but reduced for 24h. We show the binging between E2F1and MCPH1and p38 MAPK expressions. And MCPH1 regulates p38 expression in apoptosis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1221.
Management Of PICC-Associated Thrombosis In Patients Receiving Chemotherapy For Hematologic Malignancies
Authors: Meera Sridharan, Aref Al-Kali, Aneel A. Ashrani, Kebede Begna, Michelle Elliott, William J. Hogan, Carl C. Hook, Scott H. Kaufmann, Louis Letendre, Mark R. Litzow, Mrinal M. Patnaik, Animesh D. Pardanani, Ayalew Tefferi, Alexandra Wolanskyj, Rajiv K. Pruthi
Journal: Blood (2013)
Abstract 4585: Breaking metastatic dormancy during surgical resection of a primary tumor and implications for treatment strategies.
Authors: Selena R. Granitto, Amber Giles, Simon Lavotshkin, Daniel Rutigliano, David Lyden, Rosandra N. Kaplan
Journal: Cancer Research (2013)

Abstract At the time of a cancer diagnosis, most patients have localized tumors. Despite elaborate staging schemas for each cancer type in an attempt to stratify patients, the vast majority of patients that die will do so from metastatic disease. We hypothesized that surgery augments the already ongoing activation and mobilization of bone marrow-derived progenitor cells that are critical to colonizing tumor cells at distant sites. These bone marrow-derived cells, by inducing a local inflamed tumor microenvironment, provide survival signals to these seeding tumor cells. Our data show increased metastatic burden in the lung after surgical resection of the primary tumor using two murine cancer models, B16 melanoma and E0771 breast carcinoma. In these models, we also show a surge in hematopoietic and endothelial progenitor cells in the hours and days immediately following resection of the primary tumor, which is not similarly observed in control mice, where surgery was performed in the absence of the primary tumor. We also confirmed that a factor specific to the plasma of the tumor-bearing mice is responsible for this mobilization by using in vitro migration assays, whereby plasma from tumor-bearing mice and surgically resected mice induced an increased migration of lineage negative bone marrow cells compared to the plasma of wild type mice. We confirmed increased levels of MCP-1 and MCSF, both known to mobilize progenitor cells, in the plasma of mice with surgical resection. Additionally, targeting these bone marrow derived hematopoietic and endothelial progenitor cells with Pazopanib prevents the surge in bone marrow-derived cells into the circulation, abolishes the enhanced metastatic spread in mice undergoing surgical resection of the primary tumor, and provides a significant prolongation of survival. Finally, we correlated these data to a cohort of breast cancer patients where circulating levels of progenitor cells were analyzed at time points before and after surgery, which confirmed the mobilization of progenitor cells with surgery. Together, these results provide evidence for the increased risk of metastatic spread after surgical resection of the primary tumor and suggest that blocking progenitor cell mobilization by adjuvant treatment during or immediately following surgery, the incidence of metastatic recurrence may be reduced. Citation Format: Selena R. Granitto, Amber Giles, Simon Lavotshkin, Daniel Rutigliano, David Lyden, Rosandra N. Kaplan. Breaking metastatic dormancy during surgical resection of a primary tumor and implications for treatment strategies. [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 4585. doi:10.1158/1538-7445.AM2013-4585
Effect of Sodium Dextrothyroxine in Patients Receiving Anticoagulants
Authors: John C. Owens, Winston B. Neely, William R. Owen
Journal: New England Journal of Medicine (1962)

ANY new therapeutic agent brings with it the problem of identifying side effects that would not ordinarily be attributed to the particular drug. The effectiveness of dextrothyroxine in reducing serum cholesterol has been previously reported.1 , 2 Earlier, we observed that anticoagulated patients receiving this drug tended to require lower anticoagulant dosages (this has been reported by other observers3). It is the purpose of this work to investigate this effect of dextrothyroxine on the clotting mechanism.MethodsA group of 14 patients, 7 males and 7 females, were studied. Eleven of these were selected from those attending the anticoagulant clinic of . . .
Monocytes/macrophages and natural killer cells characterize the tumor microenvironment of inflammatory breast cancer in Egyptian patients.
Authors: MM Mohamed, M El-Shinawi, D Cavallo-Medved, M Sobhy, MA Nouh, SF Abdelwahab, BF Sloane
Journal: Cancer Research (2009)

Abstract Abstract #1054 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. IBC incidence appears to be higher in Egypt as compared to USA. Although the role of leukocytes in regulating breast cancer dissemination has been studied extensively, their role in IBC progression is not well understood. Previously, we showed that human monocytes augment the invasiveness and proteolytic activity of IBC cell lines. Aim: To compare the immunophenotype of IBC and non-IBC and to identify IBC tumor-infiltrated immune cell that may be associated with poor prognosis of IBC.&amp;#x2028; Methods: We enrolled two groups of patients: IBC (n=13) and non-IBC (n=27) being treated at Ain Shams University hospitals. All patients underwent modified radical mastectomy. IBC patients had 7 or more metastatic axillary lymph nodes whereas non-IBC patients had 3 or less metastatic axillary lymph nodes. During surgery, blood draining from the breast tumor microenvironment, through branches of axillary vein, and peripheral blood was collected. Total mononuclear cells were isolated from collected blood and their phenotype was examined using flow cytometry. Monoclonal antibodies specific for cell surface markers for particular cells types were used: namely T-helper cells (CD3+CD4+), T-cytotoxic cells (CD3+CD4-), natural killer (NK) cells (CD56+) and monocytes/macrophages (CD14+). Results: Within each group we compared the leukocytic composition of blood collected from the tumor drainage to that of peripheral blood in IBC and non-IBC patients. 1) In IBC, we detected a significant increase in the mean percentage of NK cells and monocytes collected from the tumor site, but no significant difference in CD8+ and CD4+ cells. 2) In non-IBC, the percentage of CD4+ T cells collected from the tumor site was significantly higher than from peripheral blood. No significant differences were detected in CD8+, CD56+ and CD14+ cells.&amp;#x2028; We compared the leukocyte composition of blood collected from both IBC and non-IBC patients. 1) In peripheral blood of IBC patients, we detected a significant increase in CD4+ T cells, but no significant differences in CD8+, CD56+ and CD14+ cells when compared to non-IBC patients. 2) When we compared the leukocyte content of blood collected from the tumor site in IBC and non-IBC, we found a significant increase in CD56+, and CD14+ cells and a significant decrease in CD4+ T cells in IBC, but no significant difference in CD8+ T cells. Conclusion: Differences in the immunophenotype of IBC versus non-IBC suggests a role for these immune cells in the metastatic dissemination and progression of IBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1054.
Stat Bite State Mammography Quality Assurance
Authors: M. McKinney, L. Fintor
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Stat Bite State Mammography Quality Assurance Get access Martha McKinney, Ph.d., Martha McKinney, Ph.d. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 8, 17 April 1991, Page 538, https://doi.org/10.1093/jnci/83.8.538-a Published: 17 April 1991
FRI0294 Biologic Monotherapy: A Treatment Option for Elderly RA Patients with Multimorbid Conditions: Table 1.
Authors: A. Richter, J. Listing, J. Kekow, S. Balzer, S. Remstedt, A. Zink, A. Strangfeld
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The treatment of RA with biologic (b)DMARDs should usually be combined with the non-biologic (nb)DMARD methotrexate (MTX). Randomized controlled trials showed superior efficacy of combination therapy in RA patients. Nevertheless, in daily clinical care about one third of patients have to be treated with monotherapy due to intolerability of MTX or other nbDMARDs. The effectiveness of this treatment regime has rarely been studied in unselected RA patients. <h3>Objectives</h3> To investigate characteristics of patients treated with bDMARDs in monotherapy versus those with bDMARDs in combination with MTX and to compare treatment adherence and comedication. <h3>Methods</h3> Patients enrolled in RABBIT with abatacept (ABA), adalimumab (ADA), etanercept (ETA) and tocilizumab (TOC) from 2007 to 2012 who had at least one follow-up (N=1937) were stratified according to their treatment with bDMARD monotherapy or bDMARD + MTX. Therapy discontinuation within the first 12 months of follow-up was examined with Kaplan-Meier methods. <h3>Results</h3> Irrespective of the particular bDMARD, patients on monotherapy were significantly older, less frequently males, had more comorbidities, poorer physical function and were more often treated with high doses of concomitant prednisone (&gt;10mg/day; p&lt;0.01). Chronic renal and liver diseases were 2 to 5 times more frequent in patients on monotherapy (p&lt;0.01; Table). There was no difference regarding treatment adherence between monotherapy and combination of bDMARDs with MTX for all agents except ADA. However, patients on monotherapy more frequently remained on higher doses of glucocorticoids after 6 months (table). For ADA, treatment continuation was significantly higher in combination with MTX (70.5/12 months [CI 65.3-75.0]) than on monotherapy (53.8 [CI 46.6-60.4]). <h3>Conclusions</h3> A considerable proportion of severely affected patients with RA cannot be treated with MTX due to comorbid conditions. This applies in particular to older and multimorbid patients who could benefit from a similarly tolerated and effective monotherapy with the bDMARDs ABA, ETA or TOC. However, it has to be kept in mind that higher dosages of glucocorticoids were needed to reach the comparable effectiveness. For ADA, combination with MTX is advisable. <h3>Disclosure of Interest</h3> A. Richter Grant/research support: The German Biologics Register RABBIT is supported by a joint unconditional grant from AbbVie, Bristol-Myers Squibb, MSD Sharp &amp; Dohme, Pfizer, Roche and UCB., J. Listing: None declared, J. Kekow: None declared, S. Balzer: None declared, S. Remstedt: None declared, A. Zink: None declared, A. Strangfeld: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3691
Abstract 1862: Capsaicin mediated activation of JNK/FOXO/BIM causes apoptosis in pancreatic cancer cells
Authors: Kartick C. Pramanik, Sanjay K. Srivastava
Journal: Cancer Research (2011)

Abstract Capsaicin, a homovanillic acid derivative (N-vanillyl-8-methyl-nonenamide) is an active component of chili pepper. We previously reported that capsaicin mediated generation of reactive oxygen species (ROS) causes apoptosis in pancreatic cancer cells. In the present study, we investigated the potential mechanism of capsaicin mediated apoptosis in pancreatic cancer cells. In a time and concentration dependent study, capsaicin treatment activated c-Jun N terminal kinase (JNK) in BxPC-3, AsPC-1 and L3.6PL pancreatic cancer cells. Further, capsaicin induced activation of JNK in turn activated FOXO1 by phosphorylating at Ser 256 and pro-apoptotic protein BIM at Ser 69. The expression of BIM also increased in response to capsaicin treatment. Capsaicin treatment also caused cleavage of caspase-9, caspase-3 and PARP resulting in apoptosis. Blocking capsaicin mediated activation of JNK by JNK-specific inhibitor SP600125 attenuated nuclear localization of FOXO-1, activation of BIM and abrogated capsaicin-induced apoptosis. To confirm the involvement of ROS in the activation of JNK, FOXO and Bim, cells were treated with antioxidants catalase and EUK (mimetic of catalase) prior to capsaicin treatment. Our results reveal that both the antioxidants blocked capsaicin mediated JNK/FOXO/BIM activation and protected the cells from apoptosis. Furthermore, silencing FOXO1 by siRNA blocked capsaicin-mediated activation of BIM and apoptosis. To further confirm the involvement of Bim in capsaicin-induced apoptosis, cells were transfected with BIM siRNA. Silencing Bim drastically reduced capsaicin-mediated cleavage of caspase-3 and PARP indicating the role of Bim in inducing apoptosis in our model. Taken together, our results suggest that ROS generated by capsaicin activates JNK and FOXO-1 which in turn activates BIM resulting in the cleavage of caspase-9/3 and PARP leading to apoptosis in pancreatic cancer cells. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute]. 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 1862. doi:10.1158/1538-7445.AM2011-1862
DIAGNOSTIC AND PROGNOSTIC UTILITY OF QUANTITATIVE CARDIAC PET EVALUATION OF CARDIAC ALLOGRAFT VASCULOPATHY
Authors: Paco E. Bravo, Tomas Vita, Viviany Taqueti, Ankur Gupta, Sara Seidelmann, Nishant Shah, Jon Hainer, Courtney Foster, Meagan Harrington, Fred Costantino, Mandeep Mehra, Sharmila Dorbala, Ron Blankstein, Michael Givertz, Marcelo Di Carli
Journal: Journal of the American College of Cardiology (2016)
Paediatric extracranial germ-cell tumours
Authors: Furqan Shaikh, Matthew J Murray, James F Amatruda, Nicholas Coleman, James C Nicholson, Juliet P Hale, Farzana Pashankar, Sara J Stoneham, Jenny N Poynter, Thomas A Olson, Deborah F Billmire, Daniel Stark, Carlos Rodriguez-Galindo, A Lindsay Frazier
Journal: The Lancet Oncology (2016)
Production and Neurotropism of Lentivirus Vectors Pseudotyped with Lyssavirus Envelope Glycoproteins
Authors: Nathalie Desmaris, Assumpcio Bosch, Christine Salaün, Caroline Petit, Marie-Christine Prévost, Noël Tordo, Pierre Perrin, Olivier Schwartz, Hugues de Rocquigny, Jean Michel Heard
Journal: Molecular Therapy (2001)

We investigated the production efficiency and the gene transfer capacity in the central nervous system of HIV-1-based vectors pseudotyped with either the G protein of the Mokola lyssaviruses (MK-G), a neurotropic virus causing rabies disease, or the vesiculo-stomatitis G protein (VSV-G). Both envelopes induced syncitia in cell cultures. They were incorporated into vector particles and mature virions were observed by electron microscopy. Vector production was two- to sixfold more efficient with VSV-G than with MK-G. For equivalent amounts of physical particles, vector titration was 5- to 25-fold higher with VSV-G than with MK-G pseudotypes on cultured cells, and in vivo gene expression in mouse brain was more intense. Thus, VSV-G pseudotypes were produced more efficiently and were more infectious than MK-G pseudotypes. Tropism for brain cells was analyzed by intrastriatal injections in rats. Both pseudotypes preferentially transduced neurons (70–90% of transduced cells). Retrograde axonal transport was investigated by instilling vector suspensions in the rat nasal cavity. Both pseudotypes were efficiently transported to olfactive neuron bodies. Thus, although coating HIV-1 particles with rabdhovirus envelope glycoproteins enables them to enter neuronal cells efficiently, pseudotyping is not sufficient to confer the powerful neurotropism of lyssaviruses to lentivirus vectors.
AB0314 Neurogenic Mechanisms of Chronic Joint Pain in Patients with Rheumatoid Arthritis and Knee Osteoarthritis
Authors: E. Filatova, E. Turovskaya, S. Erdes, L. Alekseeva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Chronic pain is the most typical clinical presentation of rheumatoid arthritis (RA) and osteoarthritis (OA). Suggest that the pain in RA and OA has mixed nature and includes nociceptive, neuropathic and psychogenic components (1,2). <h3>Objectives</h3> To study neuropathic pain (NP) in patients with RA and OA. <h3>Methods</h3> We recruited 183 patients with RA (male:female ratio 1:10) aged 18-60 years (average age 46±11.8) and 80 female patients with knee osteoarthritis (kOA) aged 45-65 years (average age 59±5) admitted to the Institute of Rheumatology. RA mean duration 9.03±7.6 years and mean duration of kOA was 9±6.5 years. Patients with chronic knee pain had OA Kellgren-Lawrence severity grade II-III. All patients underwent rheumatological and neurological examination. Patients were divided into two groups: patients with DN4 score&gt;4 (with NP) and DN4 score&lt;4 (no evident NP). <h3>Results</h3> 78 (43%) patients with active RA and 24 (30%) patients with kOA presented with NP. In the kOA group the presence of NP features was correlated with higher pain intensity, WOMAC index and significantly correlated with higher level of anxiety. Patients with NP had more diffuse hyperalgesia to mechanical stimuli compared to controls, no other somatosensory defects were found. Patients with NP and RA were older (50.1±9.4 vs. 44.4±12.8 years), had longer disease duration (10.7±8.2 years vs. 7.9±7.1 years) with a higher clinical stage (stage 3-4 92%, stage 2-3 68%) and R-stages (stage 3-4 73%, stage 2-3 84%) (p&lt;0.05). We found no significant differences between the two groups in RA activity (DAS28 score) or quality of life. Neurologic findings in patients were characterized by the presence of polyneuropathy (distal senso-motor) - 62%, tunnel neuropathy - 9%, multiple mononeuropathy - 21%, cervical myelopathy – 3%, and their combinations - 3%. <h3>Conclusions</h3> This study has demonstrated the mixed nature of chronic pain, neuropathic pain detected in 43% patients with RA and 30% with OA. Identification of neuropathic mechanisms of pain has important practical implications and opens new therapeutic perspectives for comprehensive treatment of the painful syndrome in RA and kOA. <h3>References</h3> Rheumatology, 2 edition. Edited by Academician E.L. Nosonov, Moscow. 2010; 90-231. Schaible HG, Ebersberger A, Von Banchet GS. Mechanisms of pain in arthritis. Ann N Y Acad Sci 2002:966:343-354. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2954
Carotid–Cavernous Sinus Fistula
Authors: Revadi Govindaraju, Prepageran Narayanan
Journal: New England Journal of Medicine (2016)

A healthy 18-year-old man was in a motor vehicle accident and received a head injury that resulted in intracranial bleeding at multiple sites, fractures of facial bones, and immediate traumatic mydriasis and ptosis in the left eye.
ASPIRIN WITH NON-VITAMIN K ANTAGONISTS VERSUS WITH VITAMIN K ANTAGONISTS FOR ATRIAL FIBRILLATION PATIENTS WITH INDICATION FOR ANTIPLATELETS: EVIDENCE FROM A META-ANALYSIS
Authors: Ramez S. Nairooz, Ahmed Almomani, Partha Sardar, Karam Ayoub, Waddah Maskoun
Journal: Journal of the American College of Cardiology (2016)