tbuckley/cabot-search huggingface dataset:
Abstract 1692: TRAF2 phosphorylation plays a critical role in cell adaptation to chronic oxidative stress
Authors: Hasem Habelhah, Ken Blackwell, Aliya Altaeva, Laiqun Zhang, Zhaohui Shi
Journal: Cancer Research (2010)

Abstract The tumor microenvironment is characterized by hypoxia, low glucose and oxidative stress. Cancer-cell adaptation to such chronic stress has profound consequences for malignant progression and the response to therapy. Numerous studies have demonstrated that the NF-κB signaling pathway promotes tumor progression and metastasis, whereas its inhibition sensitizes cancer cells to stress-induced apoptosis. TNF receptor associated factor 2 (TRAF2) is an adaptor protein that regulates the activation of the JNK and NF-κB signaling cascades in response to TNFα stimulation. We mapped two phosphorylation sites (Ser-11 and Ser-55) on the N-terminal RING domain of TRAF2, and reported that phosphorylation at these sites increases basal and TNFα-induced NF-κB activation. Recently we found that oxidative stress induces TRAF2 phosphorylation at both Ser-11 and Ser-55, and that this phosphorylation plays a critical role in cell survival in the context of chronic oxidative stress: cells that expressed a TRAF2 mutant in which both Ser-11 and Ser-55 are replaced by Ala (TRAF2-S11/55A) underwent apoptosis even when the cells were subjected to sublethal oxidative stress. Analysis of both JNK and IKK pathways revealed that oxidative stress induces strong and prolonged JNK, but not IKK, activation in cells expressing TRAF2-S11/55A, suggesting that TRAF2 phosphorylation promotes cell survival by inhibiting the prolonged phase of JNK activation. Importantly, TRAF2 was found to be constitutively phosphorylated in some malignant cancer cell lines, as well as in some human tumor tissues. In addition, basal TRAF2 phosphorylation is elevated in H-Ras-V12-transformed cells, and its inhibition significantly sensitized the cells to oxidative stress-induced apoptosis. These results unveil a new layer of mechanism for cancer cell adaptation to oxidative stress modulated by TRAF2 phosphorylation, and suggest that inhibiting TRAF2 phosphorylation could be a new target for anti-cancer drug development. 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 1692.
Another Embargo Broken
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Another Embargo Broken Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 6, 15 March 1989, Page 391, https://doi.org/10.1093/jnci/81.6.391 Published: 15 March 1989
A memorable patient: Reserve thy judgment
Authors: C. M Gupte
Journal: BMJ (2001)

I was a senior house officer nearing the end of my post in ear, nose, and throat surgery. It was not long since I had passed my membership examination, and I was brimming with confidence and enthusiasm. However, I regarded the weekly pre-admission clinic as a tedious routine, particularly so on this occasion as I had experienced a busy duty period on the previous night.

The patient was a 43 year old Irish man who had been listed eight months earlier by a senior surgeon. He had originally been referred to a neurologist with left sided ear pain. After several investigations, including computed tomography, he had undergone a trial of carbamazepine for glossopharyngeal neuralgia. …
Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
Authors: Salwa Suliman, Kamal Mustafa, Anke Krueger, Doris Steinmüller-Nethl, Anna Finne-Wistrand, Tereza Osdal, Amani O. Hamza, Yang Sun, Himalaya Parajuli, Thilo Waag, Joachim Nickel, Anne Christine Johannessen, Emmet McCormack, Daniela Elena Costea
Journal: Biomaterials (2016)

This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
EFFECT OF DRUGS
Authors: PAUL H. HOCH, JAMES P. CATTELL, HARRY H. PENNES
Journal: American Journal of Psychiatry (1952)

This paper discusses theoretical points of drug-induced abnormal mental states. The reaction of 3 different drugs, sodium amytal, pervitin, and mescaline, on the same individual is described and the differences noted. The relationship of personality type to drug reaction is evaluated and the normalizing and disorganizing effect of certain drugs on mental patients discussed.
AB0315 Frequency of Radiographic Procedures in Patients with Rheumatoid Arthritis:
Authors: M. Venegas Pont, C.S. Crowson, S.E. Gabriel, J.M. Davis, E.L. Matteson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) undergo radiographic investigations for disease and comorbidity evaluation. Indeed, the presence of radiographic changes in joints can be diagnostic for RA. The actual use of radiographic imaging in RA is unknown. <h3>Objectives</h3> To assess the use of imaging in RA, and assess the number and frequency of radiographic imaging studies in patients with RA versus patients without RA. <h3>Methods</h3> Study subjects were from a previously assembled population-based cohort in Olmsted County, MN, USA who fulfilled 1987 ACR criteria for RA in 1988-2007, as well as a previously identified comparison cohort of patients without RA of similar age and sex. The total number of radiographic procedures, the total person-years (py) of follow-up, the number and rates of radiographic images by anatomic sites as well as number and rate of DEXA and radionuclide bone imaging were assessed. <h3>Results</h3> 650 patients with RA and 650 patients without RA were included (mean age 55.8 years; 69% female in both cohorts). A total of 27088 radiographic procedures were performed among patients with RA and 21006 among non-RA subjects during a total of 7358 and 7597 person-years [py] of follow-up, respectively. RA patients had significantly more chest, upper extremity (UE), lower extremity (LE), bone and DEXA imaging (Table). Patients with RA also had significantly more radiographs of the spine, hip, pelvis, and sacroiliac joints (not shown). Patients with positive rheumatoid factor (RF) had more radiographic procedures than those with negative RF. Women underwent more procedures than men (Table). 57% of patients underwent hand/wrist radiographs within 1 year after RA diagnosis, but this declined to 42% during 1-3 years after diagnosis, 32% during 3-5 years after diagnosis and 28% beyond 5 years after diagnosis. The rate of utilization of hand radiographs peaked in 2001 at 45 x-rays per 100 py and subsequently declined steadily to 17 per 100 py in 2011. The rate of utilization of hand radiographs was significantly higher among women than men prior to 2002, but the rates of utilization of hand radiographs were similar in both sexes subsequently. <h3>Conclusions</h3> Patients with RA undergo significantly more radiographic procedures than persons without RA, particularly of the hands/wrist and feet. Hand X-rays are less frequently obtained in recent years, possibly reflecting clinical perception of less need due to better therapies, and lower rates of hand surgeries<sup>1</sup>.DEXA and radionuclide bone scans are more frequently done in patients with RA, likely in assessment of diagnosis and comorbidities. RF+ patients underwent more scans than RF- patients, possibly due to more severe disease in patients with positive RF. <h3>References</h3> Shourt C et al. J Rheumatol 39(3):481-5, 2012 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1573
Second-Trimester Maternal Serum Alpha-Fetoprotein Levels and the Risk of Subsequent Fetal Death
Authors: D. Kim Waller, Linda S. Lustig, George C. Cunningham, Mitchell S. Golbus, Ernest B. Hook
Journal: New England Journal of Medicine (1991)

The finding of an elevated level of maternal serum alpha-fetoprotein during the second trimester of pregnancy may indicate that the fetus has died or is about to die. It is uncertain, however, whether the finding is associated with an increased risk of fetal death later in gestation independent of known causes of elevation, such as the presence of neural-tube defects or multiple gestation.
Dingell Subcommittee Presses FDA
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Dingell Subcommittee Presses FDA Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 19, 2 October 1991, Page 1379, https://doi.org/10.1093/jnci/83.19.1379 Published: 02 October 1991
Abstract 1117: Macrophage migration inhibitory factor (MIF) plays a critical role in clear cell renal carcinoma
Authors: Bradley M. Wright, Weinan Du, Xiaofeng Li, James Finke, Brian I. Rini, Ming Zhou, Huiying He, Priti Lal, Scott M. Welford
Journal: Cancer Research (2011)

Abstract Clear cell renal carcinoma (CCRC) is the most common form of renal cancer, resulting in 50,000 new cases per year in the US, and greater than 10,000 deaths. CCRC is frequently characterized by alterations in the von Hippel-Lindau protein (VHL), an E3 ligase that mediates oxygen dependent degradation of the alpha subunit of the hypoxia inducible factor (HIF). Activation of HIF and many of its transcriptional target genes are critical for renal tumorigenesis. The macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine that has roles in inflammation, cell signaling, and cell cycle regulation. MIF is regulated by HIF, and is expressed in a variety of tumor types wherein MIF expression correlates with poor outcome. Functionally, MIF can negatively regulate p53, and thus may be particularly relevant in cancers like clear cell carcinoma in which p53 is not commonly mutated. The purpose if this study is to determine the role of MIF in CCRC. In order to determine if MIF is expressed in CCRC patient samples, we stained tumor microarrays with over 95 primary CCRC tumors for MIF expression. In keeping with its reported regulation by the VHL/HIF pathway, MIF demonstrated high expression in greater than 90% of the tumors compared to normal kidney samples. Likewise, in CCRC tumor cell lines MIF expression was highly expressed compared to cell lines in which VHL expression has been reconstituted. To determine the significance of MIF expression in CCRC tumor cell lines, MIF was depleted using two independent shRNAs and we observed significant decreases cell proliferation and clonogenic survival in a variety of CCRC cell lines. These observations were replicated by silencing the expression of the MIF receptor CD74, suggesting the MIF signaling pathway is intact and functional CCRC. At the mechanistic level, MIF is known to inhibit the function of p53 through promotion of MDM2 mediated degradation. To assess whether the role of MIF in CCRC is to regulate p53, we determined the effects on p53 signaling when MIF expression was inhibited. We found that inhibition of MIF lead to an increase in p53 stability and subsequent expression of the canonical p53 target gene p21. Together these observations suggest that MIF expression may play a critical role as a target of the HIF/VHL pathway that leads to the development of clear cell carcinoma. 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 1117. doi:10.1158/1538-7445.AM2011-1117
Replacement of Blood Loss during Surgical Procedures with Blood Collected in Citrate Phosphate Dextrose Solution
Authors: John G. Gibson, Searle B. Rees, Thomas J. MCManus
Journal: New England Journal of Medicine (1960)

THE practice of giving multiple transfusions of blood, not only for the emergency treatment of severe hemorrhage but also to meet the requirements of elective surgery involving extensive blood loss, and for priming the pump oxygenator in open-heart surgery, is increasing rapidly. Although bank blood is satisfactory in most emergencies, fresh blood is preferred in exchange transfusions and in operations involving cardiac shunt. The collection of large quantities of heparinized blood in a twenty-four-hour period imposes a burden on the blood bank, and, if not used, the blood cannot be returned to the bank for routine use and is therefore . . .
Abstract 430: Inhibition of Pin1 reduces RAD51 expression and enhances radiosensitivity in U87MG glioblastoma cells.
Authors: Edmund I. I. Chen, Chia-Hsin Ho
Journal: Cancer Research (2013)

Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor, and has poor prognosis and high recurrences. Pin1, a peptidyl-prolyl isomerase, can recognize phospho-Ser/Thr-Pro motifs and isomerize the cis/trans forms of its substrates. It has been known that Pin1 is involved in cell cycle regulation and cell proliferation, and has affected various protein stability and function, such as cyclin D1 and p53. Recent study has showed that cyclin D1 can directly bind to RAD51 upon radiation in addition to its role in cell cycle. This complex is recruited to DNA damage sites and helps DNA repair. Here, we investigated the role of Pin1 in regulating cyclin D1/RAD51 interaction and affecting the radiosensitivity in U87MG glioblastoma cells. We showed that no interaction was detected between cyclin D1 and RAD51 after ionic radiation in U87MG cells; interestingly, knockdown of Pin1 decreased both cyclin D1 and RAD51 expression and enhanced their sensitivities to radiation. Furthermore, knockdown of Pin1 with IR induced G1 and G2/M arrest which resulted in cell growth inhibition and apoptosis. Importantly, knockdown of Pin1 and combination with radiation yielded increased number of γ -H2AX foci than radiation control cells, suggesting that delayed repair occurred in pin1 knockdown cells. In summary, our results suggest that inhibition of Pin1 decreases RAD51 expression and enhances radiosenstivity in U87MG glioblastoma Cells. Citation Format: Edmund I. IT Chen, Chia-Hsin Ho. Inhibition of Pin1 reduces RAD51 expression and enhances radiosensitivity in U87MG glioblastoma 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 430. doi:10.1158/1538-7445.AM2013-430
Gastrointestinal bleeding: a peep into the future with stiffness, sprays, and sensors
Authors: S. Rana, C. Rao, D. Bhasin
Journal: Endoscopy (2012)

Gastrointestinal bleeding is a challenging emergency for the endoscopist. The improvement in endoscopic diagnosis and hemostatic techniques has radically changed the management of gastrointestinal bleeding from the administration of “tons” of antacids and emergency surgery to aggressive antisecretory therapy and application of various endoscopic injection, thermal, and mechanical hemostatic methods that reduce the need for emergency surgery. However, the efficacy of the endoscopic treatments depends upon adequate and good visualization of the lumen of the gastrointestinal tract. Nasogastrointestinal tube (NGT) insertion and gastric lavage prior to endoscopy have been shown to be safe and effective in providing better visualization of the stomach [2]. Similarly, erythromycin, a motilin receptor agonist that enhances gastric emptying by inducing antral contractions, has been shown to be more effective than placebo in providing better visualization during endoscopy [3] [4].
AB0326 Does the achievement of remission in early rheumatoid arthritis depend on the age?
Authors: P. Bradna, T. Soukup, D. Bastecka, J. Toms, M. Kodeda
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Higher age belongs to unfavorable factors in most of prognostic algorithms in rheumatoid arthritis. Aims of study were to verify the impact of age on achievement of clinical remission in early and very early rheumatoid arthritis. <h3>Methods</h3> 92 patients with early rheumatoid arthritis (ACR/EULAR criteria 2010) were treated by DMARDs according to Treat to target method. Remission was evaluated after 12 months of treatment by the DAS28≤2, 6, and according to ACR/EULAR provisional definition of remission (SDAI and Boolean methods). Low disease activity was assessed by DAS28≤3, 2. We have investigated clinical (number of swollen joints, visual scale of activity) laboratory (ESR and CRP), immunological markers (Rf's, ACPA) and x-ray of hand and foot joints. <h3>Results</h3> 49 patients were younger then 60 and 46 of them were older. Both groups get to remission in the same proportion (47 vs 51%). Patients, who reached remission, had shorter history (p=0, 03), other entry parameters were the same. Younger group had more frequently positive autoantibodies (ACPA 72 vs 26% p=0, 02; RF 90 vs 33% p=0, 03). There were more very early arthritis patients (81 vs 40%) in the younger group. Younger patients had higher entry CRP (p=0, 05) and none significantly higher ESR. In younger patients there also was higher chance to ACR/EULAR remission Boolean criteria (p=0,002) <h3>Conclusions</h3> Age in the beginning of arthritis did not affect significantly chance to achieve remission in 12 months of early and very early rheumatoid arthritis therapy. More relevant it is the time from beginning of arthritis to start of therapy; significantly better results were in first 3 months of arthritis. Younger patients, who reached remission, have more frequent autoantibodies (ACPA and RF). There was no significant difference in presence of auto antibodies between successful patients and patients, who did not achieve remission. <h3>References</h3> Hider SL, Silman AJ, Thomson W et al: Ann Rheum Dis. 2009 Jan;68(1):57-62. <h3>Disclosure of Interest</h3> None Declared
Abstract 1002: Deletion of GCN5 confers sensitivity to the histone deacetylase inhibitor CG-1521.
Authors: Ann-Christin Gaupel, Thomas J. Begley, Martin P. Tenniswood
Journal: Cancer Research (2013)

Abstract Aberrant histone post-translational modifications including acetylation are common in human cancers and result in dysregulation of gene expression. Histone acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and HDAC inhibitors (HDACi) are promising anticancer therapeutics. Our laboratory has focused on studying the effects of hydroxamic acid based HDACis including TSA, SAHA and CG-1521. We have previously shown that CG-1521 induces cell cycle arrest and apoptosis in various cell lines of breast and prostate cancer. The purpose of this study is to gain insight into the mechanism of the HDAC inhibitor CG-1521 and identify potential combinatorial drug targets. We have employed a whole genome yeast deletion library screen to determine which gene deletions confer sensitivity and resistance to CG-1521. 407 sensitive and 80 resistant strains were identified. We used gene ontology enrichment analysis to determine which pathways are modulated by CG-1521. Sensitive strains are highly enriched in processes regulating chromatin remodeling and transcription. The list of resistant strains contains many genes involved in the regulation of transcription and tRNA modification. Deletions of components of the SAGA HAT complex are highly overrepresented in the sensitive strains, including the catalytic subunit Gcn5. It appears that the SAGA complex is required to reduce the effect of CG-1521 on cell growth. Cell cycle analysis shows that CG-1521 treatment in Saccharomyces cerevisiae results in G1 arrest in both the wild type and the gcn5Δ strain. The gcn5Δ strain displays increased sensitivity to CG-1521 induced cell death compared to the wild type strain. In contrast to the highly sensitive gcn5 deletion strain, a yeast strain expressing a catalytically inactive variant of the Gcn5 protein is less sensitive to CG-1521. This indicates that functions other than the acetyltransferase activity are partially sufficient to attenuate the effects of CG-1521. We have identified that disruption of the SAGA HAT complex can sensitize cells to CG-1521 and are validating whether loss of the human Gcn5 homologs, Gcn5 and PCAF, also confers sensitivity to CG-1521 in breast cancer cell lines. Taken together, our work suggests that the combination of selective HAT and HDAC inhibitors might be effective for the treatment of cancer. Citation Format: Ann-Christin Gaupel, Thomas J. Begley, Martin P. Tenniswood. Deletion of GCN5 confers sensitivity to the histone deacetylase inhibitor CG-1521. [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 1002. doi:10.1158/1538-7445.AM2013-1002