tbuckley/cabot-search huggingface dataset:
Abstract 4277: TRAF2 is a key mediator of the EGF-induced signaling pathway.
Authors: Cong Peng, Feng Zhu, Weihong Wen, Ke Yao, Weiya Ma, Ann Bode, Zigang Dong
Journal: Cancer Research (2013)

Abstract TRAF2 plays a critical role in the mediation of the TNF-R signaling pathway toward activation of NF-κB and JNKs. Here, we reveal a novel function of TRAF2 in the epidermal growth factor (EGF) signaling pathway. Knockdown of TRAF2 blocked EGF-induced AP-1 activity and anchorage-independent cell transformation. We also showed that TRAF2 is required for RSK2 activity through RSK2 ubiquitination and that RSK2 plays a critical role in AP-1 activity mediated through CREB/c-Fos, which regulate anchorage-independent cell transformation. Citation Format: Cong Peng, Feng Zhu, Weihong Wen, Ke Yao, Weiya Ma, Ann Bode, Zigang Dong. TRAF2 is a key mediator of the EGF-induced signaling pathway. [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 4277. doi:10.1158/1538-7445.AM2013-4277
Abstract 4126: Synergism of polyamine synthesis inhibition and AMP kinase activation on human melanoma proliferation and migration
Authors: Eddy C. Hsueh, Yanping Zhang, Peng Guangyong
Journal: Cancer Research (2012)

Abstract Introduction: Metformin has been shown to inhibit human cancer cell growth via activation of MAP kinase with resultant inhibition of mTOR signaling pathway. We have reported the over-expression of ornithine decarboxylase (ODC) in human melanoma cell lines. ODC is a key enzyme in polyamine biosynthesis. We determined the effect of metformin in combination with DMFO, an ODC inhibitor, on tumor proliferation and migration, and the possible mechanisms, using human melanoma cells. Methods: Human melanoma cells were treated with Metformin, DFMO, or combination. Cell proliferation assay was performed using Cell Titer Blue proliferation assay. Cell migration assay was performed by seeding melanoma cells in 24-well plate. After overnight incubation, an artificial homogenous wound was created onto the monolayer with a plastic micropipette tip. After wounding, the migration of cells into the wound was observed at 0- and 48-hour time points. Quantitative RT-PCR for ODC1 detection was performed using Assay-on-Demand Hs00159739-ml. GAPDH served as housekeeping control. Western blotting was performed to determine the expression of AMP kinase, mTOR, p70S6K and 4E-BP1, Raf-1 and Raf-B. Data were presented as means ± SD for the three separate experiments. For comparison between groups, the student's t test was used and p&amp;lt; 0.05 was considered to be statically significant. Results: There was dose-dependent inhibition of melanoma cell proliferation and migration with either metformin or DFMO. Synergistic inhibition was observed with the combination treatment on both cell migration and proliferation. There was synergistic inhibition of ODC expression with the combined treatment compared with DFMO alone (p&amp;lt;0.01). The combination treatment also lead to significant enhancement of AMPK activation and increased phosphorylation of AMPKΨ at Thr-172 compared with metformin alone (p&amp;lt;0.01). The combination treatment resulted in inhibition of mTOR signaling with decreased phosphorylation of mTOR, p70S6K and 4E-BP1, Raf-1 and Raf-B in treated cancer cells, when compared with individual drug treatments. Conclusion: We have observed a synergistic effect of AMP kinase activation and polyamine synthesis inhibition on suppressing human melanoma proliferation and migration. The synergism is due to enhanced inhibition of both polyamine synthesis and mTOR signaling pathways. 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 4126. doi:1538-7445.AM2012-4126
Abstract 4130: Genomic profiling of ovarian tumor cell lines provides a predictive signature of sensitivity to PF-4691502, a dual PI3kinase and mTOR inhibitor
Authors: Karen E. Sheppard, Amelia Neilsen, Gwyn Ng, Joanna Chan, Richard W. Tothill, Jason Ellul, Ross D. Hannan, Ricky W. Johnstone, Grant McArthur, Wayne Phillips, Richard B. Pearson
Journal: Cancer Research (2010)

Abstract The PI3kinase/AKT/mTOR pathway plays key roles in cell growth, proliferation and survival with mTOR providing a hub for coordinating signaling in response to growth factors, hormones and nutrients. This pathway is one of the most frequently mutated or abnormally activated pathways in ovarian cancer, thus making it an excellent therapeutic target for this disease. The aims of this study were: 1. To investigate the potency of PF-4691502 (PF502) a dual PI3 kinase and mTOR inhibitor to inhibit ovarian tumor cell proliferation and induce cell death. 2. To profile exponentially growing ovarian tumor cells using gene expression, copy number variations and activation of the PI3 kinase pathway. 3. To define a predictive signature or biomarker that defines ovarian tumor cell sensitivity to PF502. A panel of 39 ovarian tumor cells were treated with PF502 (1nM-30µM) for 72h and the dose at which proliferation was inhibited by 50% (GI50) determined. Cells showed a 50-fold difference in PF502 sensitivity with GI50 values ranging from 15nM to 700nM, with the majority (85%) of cells having a GI50 of less than 200nM, these cells were classified as sensitive and the remaining 6 cell lines with a GI50 greater than 350nM were classified as resistant. PF502 also caused cell death in a subset of sensitive ovarian tumor cells. Increase in PIK3CA gene copy number was observed in 40% of the cell lines but this did not correlate with PF502 sensitivity nor did activating mutations in PIK3CA or inactivation of PTEN. Gene expression data was generated from exponentially growing cells using high-density oligonucleotide microarrays. A predictive model of response to PF502 was generated using the gene expression data. Exhaustive 10-fold cross validation of the model showed that tumour cell sensitivity could be predicted with high (96%) accuracy using approximately 20-30 genes. A differential gene expression analysis was performed using all data and 89 genes were found significantly different between sensitive and resistant cell lines. Pathway analysis revealed an over expression of inflammatory markers within the resistant class. Gene set enrichment analysis further supported an increased inflammatory signal within resistant cells, and revealed that both MYC and RAS signaling were also elevated providing a clear indication of potential targets for combination therapies in PF502 resistant disease. 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 4130.
Commentary: Management of PCB Accidents
Authors: A. Aitio, V. Riihimaki, J. Jarvisalo, J. Rantanen
Journal: Environmental Health Perspectives (1985)

The purpose of this brief note is to bring together present ideas on the prevention and management of PCB accidents. In part, this summary is based on the papers presented in the Espoo symposium, in part, it reflects our own experience on PCB accidents. Some of these matters were discussed in the Espoo meeting; however, the views presented do not represent any consensus of the participants. The present authors are solely responsible for these opinions. The primary goal in the management of PCB acci? dents is certainly prevention. To a certain extent, this goal will be achieved by exchange of PCB-containing transformers and capacitors. This, however, will only be reached in the long run; one has also to remember that the disposal of PCBs and electric devices containing them is a major problem. In addition, the safety, in? cluding fire resistance, of the substitutes has to be verified. It thus seems that PCB-containing electric appliances will be around for a long time. Of course, this is especially true of the millions of small electric appliances containing minute amounts of PCBs. Mean while, the secondary approach in prevention is prevention of PCB fires. PCB-containing equipment has to be localized; function and condition of such equipment must be regularly checked. Electric countermeasures have to be taken in order to prevent overload and harmonic currents. PCB-containing capacitors have to be situated separately from capacitors containing mineral oils. The fire burden of the locations with PCB devices has to be minimized.
P2-06-01: Genomic Instability in Breast Cancers from Atomic Bomb Survivors: An Analysis of Microarray-Comparative Genomic Hybridization with Old Archival Tissues.
Authors: M Oikawa, K-I Yoshiura, H Kondo, S Miura, T Kurashige, T Nagayasu, H Yano, M Nakashima
Journal: Cancer Research (2011)

Abstract Background: Sixty-six years after two atomic bombs (A-bombs) explosion on Hiroshima and Nagasaki, the incidence of breast cancer in A-bomb survivors still higher than that in controlled populations. We have reported a higher incidence of HER2 and C-MYC oncogene amplification in breast cancers from A-bomb survivors, which suggested genomic instability (GIN) induced by A-bomb radiation exposure might promote breast carcinogenesis in A-bomb survivors. The purpose of this study was to clarify the effect of A-bomb radiation exposure on GIN in breast cancer using microarray-comparative genomic hybridization (aCGH). Materials and Methods: DNA was extracted from the paraffin-embedded tissues of invasive ductal cancers from 11 survivors exposed at 1.5km from the hypocenter and 9 calendar year-matched non-exposed patients followed by aCGH analysis using a high-density oligonucleotide microarray (Agilent® SurePrint G3 8×60k microarray). The total length of chromosomal aberrant region was used as an indicator of GIN, and correlation with clinicopathological factors were statistically tested. Results: The mean of the derivative log ratio spread (DLRSpread), which estimates the log ratio noise by calculating the spread of log ratio differences between consecutive probes along all chromosomes, was 0.60 (range, 0.30 to 1.05). The concordance of aCGH results with FISH results for HER2 gene amplification was 90%. Samples from A-bomb survivors had significantly more copy number aberrations (CNA) than samples from control patients (P= 0.040). Samples with C-MYC gene amplification determined by aCGH analysis tended to harbor more CNA (P= 0.20), and age at the time of diagnosis tended to be inversely associated with the total length of chromosomal aberrant regions (P= 0.13). The multivariate analysis with covariance revealed that the status of A-bomb exposure was the only independent factor which was significantly associated the total length of chromosomal aberrant regions (P= 0.0324). Conclusions: This study suggested that A-bomb radiation may affect the development of chromosomal aberrant regions including oncogene amplification by inducing GIN and may be associated with a higher histological grade in breast cancer found in A-bomb survivors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-06-01.
The Bethesda System Unveiled; Revamps Pap Smear Reporting
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article The Bethesda System Unveiled; Revamps Pap Smear Reporting Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 18, 20 September 1989, Pages 1354–1355, https://doi.org/10.1093/jnci/81.18.1354 Published: 20 September 1989
Abstract 2867: Anthocyanin and carotenoid rich fresh vs. processed colored potatoes suppress human colon cancer cell proliferation and elevate apoptosis via suppression of inducible nitric oxide synthase (iNOS) pathway
Authors: Jairam Vanamala, Lavanya Reddivari
Journal: Cancer Research (2010)

Abstract The potato (Solanum tuberosum L.) is the world's 3rd largest food crop and the leading vegetable crop in the United States, with per capita consumption of about 126 lbs annually. Specialty/colored potatoes rich in anti-proliferative, pro-apoptotic and anti-inflammatory anthocyanins and/or carotenoids can be an attractive “delivery system” for these bioactive compounds in humans. Unlike other carotenoid- or anthocyanin-rich sources such as blueberries or pears, potatoes are stored and processed before consumption (80 lbs industrially processed potatoes/capita/year in the US). We previously demonstrated that colored potato extracts suppress cancer cell proliferation and induce apoptosis via both caspase-dependent and independent pathways; however, the effect of processing methods on these functional compounds is unknown. We hypothesized that potato bioactive compounds retain their chemoprotective properties against human colon cancer cells even after processing (chipping and baking) compared to the DMSO solvent controls. To test this hypothesis the anti-proliferative (WST assay), pro-apoptotic (cell death detection ELISA) and anti-inflammatory (iNOS pathway; immunoblots) properties of Atlantic (white; phenolics), Yukon Gold (yellow; carotenoids) and Purple Majesty (purple; anthocyanins) potato extracts before and after processing were determined using HCT116 p53+/+ and p53−/− human colon cancer cells. Potato extracts from processed potatoes (5 −15μg/ml) suppressed both p53+/+ and p53−/− human colon cancer cell proliferation and elevated apoptosis compared to the DMSO control after 24 hr incubation period. Similar results were observed after 48 and 72 hr of incubation. However, processing suppressed (p &amp;lt; 0.05) anti-proliferative and pro-apoptotic properties of potato bioactive compounds compared to the fresh potato extracts. Purple potato extracts were more potent in suppressing (p &amp;lt; 0.05) colon cancer cell proliferation and elevating apoptosis compared to the white and yellow colored potatoes. Potato extracts suppressed inducible nitric oxide synthase (iNOS) levels, a critical pro-inflammatory enzyme. Our results suggest that it is important to consider the processing effects on bioactive compounds in foods while conducting nutritional and epidemiological studies. We plan to determine whether colored potatoes suppress chemically-induced colon carcinogenesis in rodent models via suppression of inflammation. 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 2867.
Abstract 2941: Defining novel pathways that arrest genetically unstable tetraploid cells
Authors: Neil J. Ganem, Kevin P. O'Rourke, David Pellman
Journal: Cancer Research (2011)

Abstract Tetraploid cells, which are a common byproduct of cell division failures, are genetically unstable and have the capacity to facilitate tumorigenesis. Consequently, p53-dependent tumor suppression mechanisms exist to limit the continued proliferation of these cells by promoting G1 cell cycle arrest. However, unlike other common cellular insults that activate p53 and promote G1 arrest, such as the DNA damage response, the mechanisms governing G1 arrest in response to tetraploidy remain largely unexplored. To gain insight into these mechanisms, we have developed a novel genome-wide RNAi screening assay to comprehensively identify proteins that are necessary to activate or maintain G1 cell cycle arrest after the induction of tetraploidy. Results from this screen, in combination with complementary bioinformatic approaches, have begun to illuminate the nature of the stresses associated with tetraploidy. More importantly, this work is shedding light on the adaptive mechanisms that tetraploid and near-tetraploid tumors may have evolved in order to overcome these stresses. These findings have the potential to lead to the identification of new pathways that can be targeted by chemotherapeutics to specifically reinforce G1 arrest in grossly aneuploid cancer cells. 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 2941. doi:10.1158/1538-7445.AM2011-2941
PTU-027 Real-time Evaluation Of Oesophageal Capsule Endoscopy In Variceal Screening And Surveillance – A Pilot Prospective Study: Abstract PTU-027 Table 1
Authors: HY Lee, N Visesio, R Walmsley, A Jafer
Journal: Gut (2014)

<h3>Introduction</h3> The role of oesophageal capsule endoscopy in assessing oesophageal varices has been previously studied<sup>1</sup> where downloaded images are evaluated subsequent to study completion. This is the first study evaluating real-time viewing of oesophagogastric findings during capsule transit through the upper gastrointestinal tract for this indication. The primary aim was to assess the accuracy of real time oesophageal capsule study in identifying oesophageal varices in patients undergoing variceal screening or surveillence. Secondary aims were to establish the ability of oesophageal capsule endoscopy to detect gastric varices or portal hypertensive gastropathy, and to ascertain post procedure patient perception of comfort compared to standard gastroscopy. <h3>Methods</h3> Inclusion criteria was patients with cirrhosis referred within our centre for variceal screening or surveillance. Exclusion criteria were known dysphagia, suspected or known gastrointestinal tract stricture, suspected active gastrointestinal bleeding and active hepatic encephalopathy. Capsule assessment was performed by instructing the patient to ingest the oesophageal capsule with sips of water/simethicone mixture in left lateral patient position. Oesophagogastric mucosa was evaluated in real time during capsule transit through a computer attached to the video recorder unit using three sensor element leads. Standard gastroscopy was performed by another endoscopist, blinded to capsule findings, within the same day. Intravenous sedation was permitted during gastroscopy, if needed. Patient preference and comfort levels (by digital analogue scale where 0 = no pain, 5 = very painful) were recorded post-recovery. <h3>Results</h3> Thirty-one patients with cirrhosis (17 males, 14 females, median age 60 years) were included. There was moderate agreement level in assessing the presence of oesophageal varicose (Kappa value 0.545, p &lt; 0.005) (See table below). Majority of patients (n = 26, 84%) preferred oesophageal capsule endoscopy compared to gastroscopy. Capsule endoscopy had better mean comfort score (0.4 vs 2.0, p &lt; 0.001) even with intravenous sedation during gastroscopy in 17 (55%) patients. <h3>Conclusion</h3> Real-time viewing of oesophageal capsule potentially offers a less invasive means of variceal screening/surveillance with better patient comfort. <h3>Reference</h3> DeFranchis <i>et al</i>. Esophageal capsule endoscopy for screening and surveillance of esophageal varices in patients with portal hypertension. <i>Hepatology</i> 2008;47:1595–1603 <h3>Disclosure of Interest</h3> None Declared.
Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics
Authors: Lili Zou, Hong Wang, Bin He, Lijuan Zeng, Tao Tan, Haiqiang Cao, Xinyu He, Zhiwen Zhang, Shengrong Guo, Yaping Li
Journal: Theranostics (2016)

Cancer metastasis accounts for the high mortality of many types of cancer.Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis.In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer.PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis.Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments.We summarize the design and performance of various PTN in PTT alone and their combinational therapy.We also point out the lacking area and the most promising approaches in this challenging field.In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.
Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change
Authors: Anja Soldan, Corinne Pettigrew, Qing Cai, Mei-Cheng Wang, Abhay R. Moghekar, Richard J. O’Brien, Ola A. Selnes, Marilyn S. Albert
Journal: JAMA Neurology (2016)

<h3>Importance</h3> Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. <h3>Objective</h3> To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. <h3>Design, Setting, and Participants</h3> In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aβ and tau or Aβ and phosphorylated tau (p-tau): stage 0 (high Aβ and low tau), stage 1 (low Aβ and low tau), stage 2 (low Aβ and high tau), and suspected non-AD pathology (SNAP) (high Aβ and high tau). The data presented herein were collected between August 1995 and August 2014. <h3>Main Outcomes and Measures</h3> An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. <h3>Results</h3> Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aβ and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (β ≤ −0.06 for all and<i>P</i> ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The<i>APOE ε4</i>genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. <h3>Conclusions and Relevance</h3> These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.