tbuckley/cabot-search huggingface dataset:
Abstract LB-34: Investigating novel biological functions of tankyrases in cancer
Authors: Marie Schoumacher, Yun Feng, Yuji Mishina, Wenlin Shao
Journal: Cancer Research (2012)

Abstract Tankyrases (TNKS1 and TNKS2) are enzymes that catalyze the addition of poly(ADP-riboses) on acceptor proteins. Through poly(ADP-ribosylation), TNKS regulate the activity and/or stability of their substrates via different mechanisms. A number of TNKS substrate proteins of diverse biological functions have been reported. More recently, in silico analysis using consensus-derived TNKS binding motif predicts a wide range of proteins may be targeted by TNKS, supporting that TNKS is involved in the regulation of diverse cellular processes. In particular, TNKS have been linked to telomere elongation, Wnt signaling and spindle assembly during mitotic progression, functions that are essential for cell proliferation. Hence, TNKS could be potential molecular targets for anti-cancer therapeutics. Using highly potent and specific TNKS inhibitors or depletion of TNKS by RNAi, we have identified several cancer models which growth is dependent on TNKS activity. In one of the TNKS-dependent cancer models, RERF-LC-MS, our studies demonstrate depletion of β-catenin does not impair cell proliferation. These data suggest TNKS regulate cell proliferation in this model via Wnt-independent functions. In an effort to elucidate the mechanism underlying RERF-LC-MS growth dependence on TNKS, we tested the hypothesis whether TNKS inhibition leads to aberrant spindle formation. We observed that inhibition of TNKS increases the formation of multipolar spindles in mitotic cells. We are currently testing whether this is mediated by NuMA, a well described substrate of TNKS whose function is required for spindle integrity. In addition, we are performing proteomic studies to identify novel binding partners of TNKS that would help to unravel novel partners of TNKS in mitosis and their functions in mediating cancer cell dependence on TNKS. Overall, this work will further increase our understanding of TNKS biology in cancer, and will impact on how we could best target TNKS as a novel anti-cancer treatment. 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 LB-34. doi:1538-7445.AM2012-LB-34
High Expectations for Colony-Stimulating Factors
Authors: L. Schwab
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article High Expectations for Colony-Stimulating Factors Get access Linda Schwab Linda Schwab Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 7, 3 April 1991, Pages 470–471, https://doi.org/10.1093/jnci/83.7.470 Published: 03 April 1991
P447Amelioration of myocardial ischaemia /reperfusion injury by DITPA via modulation of apoptosis and inflammation
Authors: N R Hadi, F G Alamran, M G Yousif, K Mohsin
Journal: Cardiovascular Research (2014)

Background: The importance of apoptosis in cell death following ischemia and reperfusion has been demonstrated in vivo rodent models,. Thyroid hormone can have positive effects on the cardiovascular system but its therapeutic potential is limited secondary to its adverse effects. DITPA has been shown to reduce pathologic remodeling and improve cardiac output following myocardial infarction.
Abstract 3445: The role of p38/MAPK14 in cerebellar granule neuron precursor proliferation and medulloblastoma
Authors: Cemile G. Guldal, Lori A. Mainwaring, Anna M. Kenney
Journal: Cancer Research (2011)

Abstract Development of the cerbellum occurs primarily postnatally and is marked by a rapid proliferation of cerebellar granule neuron precursors (CGNPs). This proliferation requires the activity of the mitogen Sonic Hedgehog (Shh). CGNPs are proposed to be the cells of origin for some classes of medulloblastoma (MB), the most common solid pediatric tumor, making their proliferation an attractive target for cancer therapy. Since MAP kinases play important roles in many aspects of development, proliferation, and cancer, we investigated if any of the three major classes of MAP kinases were involved in Shh-driven CGNP proliferation. We have previously shown that p42/p44 ERK MAP kinases are not involved in Shh signaling in CGNP proliferation. We have also shown that JNK/SAP kinases are not involved in Shh-driven proliferation. However, p38/MAPK14 is induced and activated in proliferating CGNPs compared to CGNPs that exit the cell cycle and differentiate in the absence of Shh. Other known pathway components upstream and downstream of MAPK14, such as ASK1, MKK3 and ATF-2, are also activated in the presence of Shh. Antioxidants such as lipoic acid and n-acetyl-cysteine that relieve oxidative stress reduced Shh-induced activation of MAPK14 and caused a marked decrease in CGNP proliferation measured by Ki67 and BrdU staining. Knocking down p38 in CGNPs also causes a marked decrease in Shh-dependent proliferation and an increase in apoptosis, which indicates a role for MAPK14 in CGNP survival. We are currently investigating the mechanism of Shh regulation of p38 MAPK pathway, which will lead to a better understanding of CGNP proliferation, cerebellar development, and MB progression. 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 3445. doi:10.1158/1538-7445.AM2011-3445
SAT0356 Prevalence and severity of depression in postmenopausal women with osteoporosis
Authors: H. Bahouq, F. Allali, I. Hmamouchi, S. Alioualla, N. Hajjaj Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Multiple studies have reported an association between depression and low bone mineral density. However, prevalence and severity of depression in postmenopausal women with osteoporosis are lacking. <h3>Objectives</h3> The objective of this study was to determine the prevalence and severity of depression in postmenopausal women with osteoporosis and to identify eventual factors associated with this depression. <h3>Methods</h3> In this cross sectional study, One hundred women with osteoporosis were included (mean age: 61.8±8.4 years). Patient Health Questionnaire-9 was used for the assessment of the severity of depression with 5 degrees of severity (minimal, mild, moderate, moderately severe and severe depression). ECOS-16 quality of life questionnaire was used to evaluate the quality of life of patients. Eventual relationship between depression, osteoporosis and patients characteristics was analyzed. <h3>Results</h3> Eighty nine percent of our patients are suffering from depression. Depression was minimal, mild, moderately severe and severe in respectively 40, 22, 19, 13 and 6%. Severity of depression was correlated with a decreased bone mineral density of the lumbar spine (r= -0.24; p=0.01), a bad quality of life (r=0.58; p&lt;0.0001) and a global pain measured by visual analogical scale (r=0.43; p&lt;0.0001). Multiple logistic regression models have shown that only quality of life of patient (OR=11.520; IC 95% (1.019- 13.270); p=0.04) was the significant independent factor related to depression severity. <h3>Conclusions</h3> Our data suggests that in postmenopausal women with osteoporosis, prevalence of depression is considerable. Also, severity of this depression depends closely on the quality of life of those patients. In consequence, assessment of osteoporosis in postmenopausal women must consider the quality of life of patients and the severity of depression in guiding treatment decisions. Further studies on large samples are needed to confirm those results. <h3>Disclosure of Interest</h3> None Declared
PET Appearance of Tuberculous Empyema Necessitans
Authors: Matthew P. Lungren, Jared D. Christensen, R. Edward Coleman, Rajan T. Gupta
Journal: Clinical Nuclear Medicine (2011)

A 28-year-old man with no medical history presented with right-sided swelling of the chest. Findings from the CT scan revealed multiple subcutaneous cystic masses and cavitary lung lesions. FDG PET imaging demonstrated hypermetabolic cavitary lung lesions and cyst walls with no central uptake. Polymerase chain reaction fluid analysis confirmed the growth of Mycobacterium tuberculosis. Operative incision and drainage yielded 2.5 L of purulent material. First described in the 17th century, the hallmark presentation of empyema necessitans is anterior chest wall soft-tissue swelling. M. tuberculosis remains its most common cause. Extraparenchymal collections begin with tuberculosis pleuritis followed by caseous material eroding through the chest wall into fascial planes.
Follicular Thyroid Adenoma Showing Avid Uptake on 68Ga PSMA-HBED-CC PET/CT
Authors: Gowri L. Kanthan, James Drummond, Geoff Paul Schembri, Michael A. Izard, Edward Hsiao
Journal: Clinical Nuclear Medicine (2015)

68Ga-prostate-specific membrane antigen (PSMA) PET/CT imaging is a relatively new imaging technique used to evaluate the extent of disease in prostate carcinoma. Various other neoplasms may also express PSMA and show uptake on PSMA PET/CT scan. We report a case of a 62-year-old man who had a PSMA PET/CT scan for restaging of prostate carcinoma. A PSMA-avid thyroid lesion was identified, and subsequent tissue sampling confirmed the diagnosis of follicular thyroid adenoma. It is important to be aware of this possibility to avoid scan misinterpretation. Tissue biopsy of PSMA-avid thyroid lesions should be considered to exclude a primary thyroid neoplasm.
Organic Osmolytes in the Brain of an Infant with Hypernatremia
Authors: Jung Hee Lee, Edgardo Arcinue, Brian D. Ross
Journal: New England Journal of Medicine (1994)

Neurologic symptoms due to electrolyte disorders are common, occurring in patients with diarrhea, diabetes mellitus, head injury, renal failure, and many other disorders, especially in infants and the elderly. The clinical syndromes of dehydration and overhydration, often first detected in measurements of plasma sodium or osmolality, are among the most frequent causes of the neurologic symptoms, which include irritability, seizures, lethargy, and coma. There are multiple hormonal and neurogenic mechanisms to maintain total body water and the concentration of solutes (osmolality) within narrow limits. Interruption of these homeostatic mechanisms leads to the retention or loss of either water or solute; . . .
SP0177 An RMD Senior Facing Life Working Challenges with Professionalism
Authors: M. Dobrin
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The abstract is a short presentation of how the subject is to be treated and it contains the main elements of the aforementioned lecture with the key messages to be shared with the delegates and participants. I have been diagnosed with the RA - rheumatoid arthritis disease in April 2004 and since then I had to cope with different symptoms and to follow different treatments within the hospital and at home. The following main aspects will be treated within the lecture: Environmental and working conditions, main and collateral symptoms before the RA manifested. The main findings, the diagnostic and the very first approach to treatment. Different symptoms and different treatment approaches. Biologic treatments in my case: type, symptoms, efficacy. How Rheumatoid Arthritis affected my life during the last 10 years? Conclusions &amp; Key messages to be shared with the delegates and participants <h3>Disclosure of Interest</h3> M. Dobrin Consultant for: Romanian EULAR League <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6125
Abstract 1932: Bortezomib sensitizes malignant human glioma cells to histone deacetylase inhibitors depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation and Mcl-1 cleavage
Authors: Daniel R. Premkumar, Esther P. Jane, Naomi R. Agostino, Ian F. Pollack
Journal: Cancer Research (2011)

Abstract Glioblastomas are invasive tumors with poor prognosis despite current therapies. Unfortunately, individual targeted therapies have failed to offer long-term survival benefit. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth. Suberoylanalide hydroxamic acid (SAHA, vorinostat) and LBH-589 are inhibitors of several members of the HDAC family, and we and others have noted some antiglioma activity, although insufficient to warrant use as single-agent therapy. Proteasome inhibitors represent a promising class of anticancer agents, already in clinical use, as bortezomib (PS-341/Velcade) has been approved for the treatment of multiple myeloma with inactivation of NF-κB signaling pathway. We have recently demonstrated that bortezomib exhibited potent anti-glioma activity and dramatically sensitized highly resistant glioma cells to TRAIL cytotoxicity, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. These studies showed that bortezomib enhanced vorinostat and LBH-589-induced apoptosis in malignant glioma cells. Although vorinostat or LBH-589 treatment alone did not induce apoptosis in glioma cells, efficacy was enhanced by addition of bortezomib, which promoted activation of proapoptotic mitochondrial injury, generation of ROS, and inhibition of the prosurvival NF-κB signaling pathway. Our results also revealed that cotreatment with bortezomib and vorinostat enhanced apoptosis by increasing Mcl-1, Noxa cleavage and other pro-apoptotic protein expression. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. 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 1932. doi:10.1158/1538-7445.AM2011-1932
Abstract 1910: 3′UTR poly(T/U) tract deletions and altered expression of <i>EWSR1</i> are a hallmark of mismatch repair-deficient cancers.
Authors: Salvatore Piscuoglio, Shivendra Kishore, Michal Kovac, Annette Gylling, Friedel Wenzel, Francesca Trapani, Hans Joerg Altermatt, Valentina Mele, Giancarlo Marra, Päivi Peltomaki, Luigi Terracciano, Mihaela Zavolan, Karl Heinimann
Journal: Cancer Research (2013)

Abstract Background: Microsatellite instability (MSI), the genome-wide accumulation of DNA replication errors, is the hallmark lesion of DNA mismatch repair (MMR) deficient cancers, present in Lynch syndrome (LS)-related and 10-20% of sporadic colorectal (CRC), gastric and endometrial cancers. MSI testing is widely used to guide clinical management but the functional significance of MSI at distinct genic loci remains largely elusive. Here, we characterize a novel MSI target locus consisting of a mononucleotide (T/U)16 tract located in the 3’untranslated region (UTR) of the Ewing sarcoma break point region 1 (EWSR1) gene (EWS16T). Methods: The diagnostic accuracy of EWS16T to identify MMR-deficient cancers was determined by analyzing 319 cancers (240 colorectal, 72 gastric, 7 endometrial) from two different populations. The functional consequences of EWS16T contractions were assessed in vitro (siRNA-mediated poly(A) site selection and pull-down assays) and in vivo (mRNA and protein expression by qPCR and tissue microarray analysis). Results: The EWS16T locus discriminates MMR-proficient (n=128) from deficient (n=191) cancers with perfect diagnostic sensitivity (100%) and specificity (100%). Biochemical analyses indicate that EWS16T contractions alter poly(A) site selection by promoting SFPQ-mediated distal poly(A) site usage in EWSR1 pre-mRNAs and result in decreased mRNA as well as EWS protein expression. In contrast to their MMR-proficient counterparts (n=64), MMR-deficient, LS-related CRC (n=94) display altered subcellular localization of EWS (p&amp;lt;0.001). Conclusions: The EWS16T locus represents a novel, quasi-monomorphic MSI target locus to accurately identify both hereditary and sporadic MMR-deficient cancers. Contractions therein affect multiple regulatory mechanisms implicating the RNA-/DNA-binding Ewing sarcoma protein in MSI-associated colorectal tumorigenesis. Citation Format: Salvatore Piscuoglio, Shivendra Kishore, Michal Kovac, Annette Gylling, Friedel Wenzel, Francesca Trapani, Hans Joerg Altermatt, Valentina Mele, Giancarlo Marra, Päivi Peltomaki, Luigi Terracciano, Mihaela Zavolan, Karl Heinimann. 3′UTR poly(T/U) tract deletions and altered expression of EWSR1 are a hallmark of mismatch repair-deficient 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 1910. doi:10.1158/1538-7445.AM2013-1910
Characterization of the HER2 status on circulating breast cancer cells.
Authors: C Alix-Panabières, S Riethdorf, T Fehm, J Vendrell, K Pantel
Journal: Cancer Research (2009)

Abstract Abstract #5018 Background: Detection and characterization of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients could help to guide treatment decisions before the onset of overt metastasis as well as in the setting of advanced disease. The HER2 oncogene is the most prominent therapeutic target in breast cancer and shedding of the extracellular domain of this receptor seems to contribute to constitutive activation of HER2. Here we developed a novel assay to detect shedding of the extracellular domain (ECD) of the HER2 oncogene on single CTC and applied this assay to the analysis of blood from metastatic breast cancer patients.&amp;#x2028; Material and Methods: Using a new dual fluorescent CK19/HER2-EPISPOT assay, the shedding of HER2 ECD by CTC from 49 metastatic breast cancer patients was assessed. In parallel, using the CellSearch system, the number of CTC and their HER2 expression were determined on 42 samples from metastatic breast cancer patients. A subgroup (n=34) of these patients was analyzed with both methods. This work was performed in the context of the activities of the DETECT study group.&amp;#x2028; Results: In the CK19/HER2-EPISPOT assay 24 of 49 (48.9%) patients had CTC (mean, 12.4; median, 5; range 1-141) and among these positive patients, 7 of 24 (29.2%) showed also HER2-secreting CTC (mean, 3.3; median, 2; range, 1-14). Using the CellSearch™ system, in 23/42 (54.8%) patients CTC were found (mean, 82; median, 13; range, 1-656). HER2 staining intensity was heterogeneous even among CTC from the same patient. Regarding the samples analyzed with both methods, we found that 23.5%, 50.0%, 50.0% and 76.5% of the patients were positive with both detection methods, the EPISPOT assay only, the CellSearch™ system only and one or the other method, respectively.&amp;#x2028; Discussion: These findings demonstrate, for the first time, that (i) CTC can secrete HER2 and (ii) HER2 secretion is not closely linked to HER2 CellSearch™ status. Both assays (i.e., EPISPOT and CellSearch™) have a comparative sensitivity and appear to be complementary for the detection and characterization of the HER2-status of CTC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5018.
Omeprazole Has Anti-Inflammatory Effects on Type 2 Cytokine-Stimulated Human Airway Epithelial Cells
Authors: Jin Young Min, Robert C. Kern, Christopher J. Ocampo, Tetsuya Homma, David B. Conley, Stephanie Shintani-Smith, He Huang, Lydia Suh, James E. Norton, Kathryn E. Hulse, Atsushi Kato, Robert P. Schleimer, Bruce K. Tan
Journal: Journal of Allergy and Clinical Immunology (2015)
BEAM-alemtuzumab followed by allogeneic SCT for the treatment of relapsed or refractory T-NHL
Authors: R. Repp, A. Günther, H. Schade, A. Humpe, B. Gahn, M. Nickelsen, A. Claviez, A. Schrauder, M. Gramatzki
Journal: Journal of Clinical Oncology (2008)

8552 Mature T/NK-cell-Lymphomas represent highly malignant and in Western countries rare tumors of lymphoid origin. For patients with relapsed or refractory T-NHL the prognosis is grim and no standard treatment strategy exists. Ten patients (age: 11 to 59 y) with relapsed or refractory T/NK-NHL were treated with allogeneic stem cell transplantation (SCT) after 1 to 2 cycles of CLAEG (cladribine, cytarabine, etoposide and G-CSF) induction therapy followed by conditioning with BEAM (carmustine, cytarabine, etoposide, melphalan) combined with alemtuzumab (Campath-1H). The following subtypes were included: 5 peripheral T-NHL (NOS), 2 angioimmunoblastic, 1 ALK negative ALCL, 1 extranodal NK/nasal type and 1 enteropathy-type T-NHL. All patients had at least 2 different treatment regimens previously. After induction chemotherapy with CLAEG, one patient achieved a CR, 6 PR and 3 SD. 7 patients received peripheral blood stem cells from HLA-identical unrelated donors and 2 from matched sibling donors. 1 patient received bone marrow from an one-allele mismatched unrelated donor. Engraftment was rapid and the treatment well tolerated. There were 4 cases of grade IV mucositis, 2 cases of sepsis in neutropenia, and 1 case of grade IV liver toxicity. One patient died from sepsis on d + 45. Prophylaxis for graft-versus-host disease (GvHD) consisted of cyclosporine A and MTX or mycophenolate mofetil. No grade III or IV acute GvHD was seen and only 3 patients presented with grade II GvHD. Two patients experienced limited chronic GvHD. Asymptomatic CMV reactivation was found in 4 cases and all were treated successfully. Late infections occurred in four patients, including CMV infection, viral enteritis, aspergillosis and streptococcal sepsis. 9 patients achieved a CR after allogeneic SCT. Currently, 3 patients relapsed: two of them died due to disease-related complications, one is receiving DLI. Another patient died in CR on day + 233 due to aspiration pneumonia caused by non-malignant bowel stenosis. All other patients remained in CR for up to 27+ months. Allogeneic SCT with this strategy shows a surprisingly good outcome in a group of T/NK-NHL patients with an otherwise very poor prognosis and seems to be a promising therapeutic option for these patients. No significant financial relationships to disclose.
Bone-Marrow Mast Cells in Osteoporosis of Aging
Authors: Boy Frame, Robert K. Nixon
Journal: New England Journal of Medicine (1968)

Of 135 women beyond fifty years of age who were evaluated for levels of bone density, those with a normal or only a minimally decreased bone density had the highest number of normal bone-marrow mast-cell counts. In contrast, increased numbers of mast cells occurred in patients with a moderate to marked decrease in bone density. It is possible that bone-marrow mast cells and heparin, which is synthesized by mast cells, play an important part in the pathogenesis of age-related osteoporosis.
PREOPERATIVE ANEMIA, THYROXINE LEVELS, CREATININE CLEARANCE AND BETA-BLOCKER USE ARE ASSOCIATED WITH THE DEVELOPMENT OF VASOPLEGIA AFTER HEART FAILURE SURGERY
Authors: Marieke van Vessem, Meindert Palmen, Lotte Couperus, Bart Mertens, Laurens Tops, Harriette Verwey, Robert Klautz, Martin Schalij, Saskia Beeres
Journal: Journal of the American College of Cardiology (2016)