tbuckley/cabot-search huggingface dataset:
Abstract 3585: Nicotine contributes to oral cancer by promotion of cell invasion through ASAP1 signaling pathway.
Authors: Chang Hsu Chiang
Journal: Cancer Research (2013)

Abstract Oral cancer is characterized as prolonged exposure to potential risk factors, including tobacco use or cigarette smoking. However, the underlined mechanism of tobacco leads to cancer is still largely unknown. To shed light on the molecular basis of tobacco induced oral carcinogenesis, we established three sublines of oral cancer cells chronically treated with nicotine (IC30 dose for 3 months). Phenotypic characterization showed that the sublines were tolerant to nicotine, increased cell invasion and migration abilities, along with the altered expressions of epithelial-mesenchymal transition markers. The transcriptomic profiling analysis was performed between parental and the subline cells to global survey and identify nicotine induced genes. Heretical clustering analysis reveals that 1004 genes were differentially expressed, in which 28% of the genes associated with cell mobility. Total of 13 genes were confirmed by RT-PCR assay that over-expressed in the nicotine sublines. ASAP1 was significantly increased in all 3 cell lines, and it was selected for further studied. Knockdown ASAP1 expressions by shRNA reduced nicotine induced cell migration (to 60% ∼ 80%) and invasion (to 55% ∼ 60%) abilities. This ASAP1 silencing further inhibited nicotine- induced MMP2 enzyme activity. Clinical study also supported this finding that ASAP1 was significantly elevated in the oral cancer tissues from patients with smoking habits (P=0.042) but not in the cancer patients without smoking (P=0.714). We therefore concluded that tobacco contributes to oral cancer by the promotion of cell migration and invasion, which was at least in part, through ASAP1 associated signaling pathway. Citation Format: Chang Hsu Chiang. Nicotine contributes to oral cancer by promotion of cell invasion through ASAP1 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 3585. doi:10.1158/1538-7445.AM2013-3585
607 PHASE 1/2A STUDIES WITH OCR-002 (ORNITHINE PHENYLACETATE); OPTIMIZED DOSING REGIMEN WITH AN AMMONIA SCAVENGER FOR TREATMENT OF HEPATIC ENCEPHALOPATHY
Authors: T. Hassanein, J.P. Kittrelle, J. Cato, L. Fischer, K. Anderson
Journal: Journal of Hepatology (2012)
Abstract P1-11-23: Cannabinoid Receptor 2 Compounds in the Attenuation of Breast Cancer Cell Proliferation: Mechanisms of Action
Authors: KE Hanlon, AN Lozano-Ondoua, A Chandramouli, TM Largent-Milnes, PJ Umaretiya, DJ Stapleton, MA Nelson, PW Mantyh, TW. Vanderah
Journal: Cancer Research (2010)

Abstract Cannabinoids have been well established as mediators of tumor cell proliferation in several cancer models. The activity of cannabinoid receptor 1 (CB1) agonists as well as cannabinoid receptor 2 (CB2) agonists have been extensively studied over the last decade, though their mechanisms of action have yet to be defined in the context of attenuating tumor proliferation. CB1 is abundant in the central nervous system with a low level of expression in the periphery, while CB2 exists primarily on cells of the immune system. Due to the lack of neuronal expression of CB2 receptors, compounds acting at CB2 receptors do not produce the psychotropic effects associated with CB1 receptor compounds. Although CB1 and CB2 compounds have yielded similar antiproliferative results in some tumor cells in vitro, CB2 receptors are markedly upregulated in many tumor cell lines for unknown reasons. Therefore, we focused on compounds selective for the CB2 receptor, including the CB2 selective agonists JWH-015 and AM1241. We show here that CB2 agonists and antagonists alike attenuate the proliferation of mouse and human breast cancer cells in a concentration dependent manner. CB2 agonist induced breast cancer anti-proliferation is not blocked by pretreatment with pertussis toxin, the CB1 cannabinoid receptor antagonist SR141716, or the transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist capsazepine. The CB1 and CB2 receptors are classified as G-protein coupled receptors (GPCRs) that are generally linked to Gai or Gaq. Agonists and antagonists of G protein coupled receptors are typically defined based on their Ga mediated effect on intracellular cAMP levels. This method of classification is not entirely effective: it ignores the possibility of differential effects on alternative kinases and the bg subunit activity. The anti-proliferative activity of both JWH-015 and SR144528 may be explained by alternative receptor coupling pathways, changes in constitutive activity, or activity at a separate receptor. Here, we show a dose and time dependent decrease in phosphorylated ERK in cells treated with either JWH-015 (CB2 agonist) or SR144528 (CB2 antagonist). Together, these data along with the absence of a pertussis toxin effect suggest that the CB2 compounds are acting in a non-Gai coupled manner, and are attenuating a pro-survival pathway. Further studies are necessary to identify the binding partner responsible for the antiproliferative effects of CB2 compounds. We advance the idea that CB2 receptors on breast cancer cells constitutively activate the MAP/ERK pro-survival pathway and that by preventing constituitive activity of the CB2 receptor, CB2 compounds downregulate phosphorylation of the MAPK/ERK pathway to promote apoptosis of breast cancer cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-23.
Abstract P3-06-16: Predictive biomarker of pathologic complete response to neoadjuvant chemotherapy in triple negative breast cancer
Authors: T Kim, W Han, H-G Moon, D-Y Noh
Journal: Cancer Research (2012)

Abstract Neoadjuvant chemotherapy has been considered valuable beyond its role in facilitating conservative surgery and improving prognosis associated with pathologic complete response. Predictive factors of response would help to assess the expected individual benefit of this treatment. Bcl-2 and p53 have been mostly investigated predictive biomarker for the efficacy of chemotherapy in breast cancer, however, studies documenting predictive significance of biomarkers in triple negative breast cancer(TNBC) are limited by low n values of patients. Furthermore, studies did not provide consistent result to conclude about predictive value of biomarkers. There is no unique explanation to date to account for such inconsistencies across studies. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 and p53, have been evaluated to assess whether they may play a role in modulating response to triple negative breast cancer to neoadjuvant chemotherapy. From January 2003 to December 2011, 187 patients presenting T1-4 N0-3 M0 primary TNBC were submitted to two different chemotherapeutic regimens before surgery. The first 154 received the doxetaxel/doxorubicin regimen, the remaining 33 were submitted to doxorubicin and cyclophosphamide followed by doxetaxel. The expression of p53, bcl-2 was evaluated in TNBC specimens obtained at diagnosis by core needle biopsy and at postchemotherapy surgery. Overall pathologic complete response(pCR) occurred in 43 of the 187 cases(23%). The pCR rate was superimposable in the patient subgroups with bcl-2-positive or –negative primary tumors. Conversely, p53 expression was significantly associated with higher pCR rate(19.5 vs 73.2%; p = 0.026; in patients with p53- and p53+ breast cancer). In a multivariate regression analysis, after adjusting for tumor and node status, treatment administered, p53 status maintained an independent predictive role for pCR.[relative risk(RR)=6.247, 95% confidence interval (CI)=0.9–39.1] In our homogeneous patient population, pCR was not associated with initial clinical stage, nodal status as well as other clinicopathologic factors. The status of the p53, which is mutated in a high percentage of breast tumors, is a predictive factor for cytotoxic drug activity. By contrast, bcl-2 failed to be related to chemotherapy activity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-16.
Abstract LB-256: Targeting MLL1 methyltransferase activity for treatment of acute leukemia with MLL1 rearrangement
Authors: Elizabeth C. Townsend, Fang Cao, Hacer Karatas, Shao-Meng Wang, Yali Dou
Journal: Cancer Research (2012)

Abstract Translocation of the MLL1 gene, which encodes for the histone methyltransferase, MLL1, is found in approximately 10% of all cases of acute leukemia and is generally associated with poor patient outcomes. Recent research has pointed to an essential function for the wild-type copy of MLL1 in these leukemias. In these cells, abnormal upregulation of MLL1-directed histone methylation and subsequent overexpression of MLL1 gene targets is an essential step in the development and progression of leukemia. Efficient MLL1-catalyzed histone methylation can only be achieved when MLL1 associates with the complex of WDR5, RbBP5 and Ash2L. MLL1 complex assembly is nucleated by a highly conserved interaction between the MLL1 SET domain and WDR5. We hypothesize that blocking histone methyltransferase activity of wild-type MLL1 through inhibition of the essential WDR5-MLL1 interaction will prevent abnormal gene upregulation and transformation in leukemias with MLL1 rearrangement. Using rational design, we have developed potent inhibitors for WDR5. We have demonstrated that the lead compound, MM-401, can disrupt the interaction of MLL1 with WDR5, and prevent assembly of the MLL1 complex. We have also shown that MM-401 specifically inhibits MLL1 complex activity, with an IC50=320nM. Using MLL1 fusion-transduced mouse bone marrow cells as a model, we have shown that treating leukemia cells with MM-401 inhibits expression of the MLL1 target oncogene, HoxA9, in a concentration-dependent fashion. Treatment of these cells with MM-401 also promotes differentiation of leukemia blasts in a dose dependent manner. Furthermore, MM-401 specifically impairs cell growth and viability of human leukemia cell lines with MLL1 rearrangement but does not alter growth of leukemia cell lines with mutations or translocations targeting other oncogenes. In conclusion, we have developed a potent inhibitor MM-401, which is the first in a novel class of inhibitors designed to target MLL1 methyltransferase activity, one of the most important chromatin modifying enzymes for transcription activation. We have further demonstrated that pharmacological inhibition of the MLL1 methyltransferase activity specifically targets leukemias with MLL1 rearrangement, and shifts leukemia cells away from the undifferentiated, rapidly proliferating state that is characteristic of aggressive AMLs. These results point to a promising new therapeutic target for leukemia 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-256. doi:1538-7445.AM2012-LB-256
A Survey of Food Intolerances in Hospitalized Patients
Authors: James P. Koch, Robert M. Donaldson
Journal: New England Journal of Medicine (1964)

IT is commonly believed that gastrointestinal symptoms may be produced in otherwise healthy people by the ingestion of certain foods. In addition specific foods are often thought to initiate or aggravate symptoms of various gastrointestinal disorders. Some of these beliefs are so widely held that they have attained the status of "knowledge" and form the basis for dietary therapy. Thus, everyone "knows" that foods rich in fats cause distressing symptoms in patients with biliary-tract disease and that proper management of such patients includes a diet low in fat content. Neither the popularity nor the intensity of such convictions, however, appears . . .
P23 Comparison of enhanced liver fibrosis test and transient elastography for the non-invasive assessment of liver fibrosis in chronic hepatitis B
Authors: P. M. Trembling, P. Lampertico, J. Parkes, S. Tanwar, M. Viganu, F. Facchetti, M. Colombo, W. M. Rosenberg
Journal: Gut (2011)

<h3>Introduction</h3> The enhanced liver fibrosis (ELF) test comprises a panel of biomarkers of liver fibrosis shown to accurately assess fibrosis and predict clinical outcomes in a range of chronic liver diseases. This is the first study of performance of ELF in patients with chronic hepatitis B (CHB) using a single aetiology cohort, and we compare its performance with an alternative method of assessing fibrosis, transient elastography (TE). <h3>Aim</h3> We aimed to compare the performance of ELF with transient elastography (TE) in a cohort of patients with CHB, in the identification of liver fibrosis using liver biopsy as the reference standard. <h3>Method</h3> 188 patients with CHB were recruited consecutively at a single Italian centre. TE, serum sampling and liver biopsy were performed on the same day. ELF tests were performed in one batch at a central laboratory using thawed samples previously stored at −20°C. Biopsies were assessed by one pathologist using the Ishak staging system. Diagnostic performance of ELF and TE for detection of histological stages of liver fibrosis was assessed and area under receiver operator characteristic curves (AUROC) calculated. Only those in whom TE was successfully performed were included. Different fibrosis levels were assessed, from any fibrosis (0 vs 1–6) to cirrhosis (0–4 vs 5, 6 and 0–5 vs 6). <h3>Results</h3> Patients were treatment-naive, median age was 47 years. 78% were e-antigen negative. Biopsies reported mild/moderate fibrosis (Ishak 0–1) in 21%, moderate fibrosis (2–3) 41% and severe fibrosis/cirrhosis (4–6) 38%. ELF and TE demonstrated good performance in identifying fibrosis (Abstract P23 table 1—representative fibrosis stages are shown, further data available). Both modalities showed similar performance in identifying any fibrosis and minimal fibrosis, with TE performing better in identifying moderate and severe fibrosis, and cirrhosis. <h3>Conclusion</h3> In untreated patients with CHB with moderate and severe fibrosis or cirrhosis, TE correlated more closely with histological staging than ELF. The relatively modest performance of ELF in detecting severe fibrosis compared to previous studies may be attributable to disease aetiology or prolonged sample storage at −20°C. Further validation of TE and ELF in CHB should include analysis at the time of sampling and evaluation of the prognostic performance for clinical outcomes as well as histology.
Abstract P4-01-09: Screening breast magnetic resonance imaging (MRI) in early-stage breast cancer survivors
Authors: AA Dowton, ME Meyer, KJ Ruddy, ED Yeh, AH Partridge
Journal: Cancer Research (2012)

Abstract Background: Limited evidence is available regarding the value of screening breast MRI in female early stage breast cancer survivors. We sought to evaluate outcomes of index screening breast MRI in breast cancer survivors in the modern era of breast cancer treatment and imaging. Methods: Using a large prospective institutional database, we identified all women who underwent breast MRI between 7/2006 and 6/2008, were ≥ 1 year and ≤ 3 years after diagnosis of stage I-IIIa breast cancer, had remaining breast tissue after treatment, and had consented to a record review protocol at our center (95% uptake rate). Sociodemographic, disease, staging and treatment information (see table 1), indications and outcomes for breast MRI, as well as disease status at 2 years after the index MRI were ascertained. Results: 643 patients were identified as having undergone at least 1 MRI of the breast(s); 248 (38.5%) were diagnostic MRIs (had identified clinical indication or imaging abnormality); 12 (2%) were missing clinical data; 383 (59.5%) were screening MRIs. 338/383 (88%) patients who had screening MRI had stage I-IIIa invasive breast cancer. 220/338 (65%) MRIs performed were index MRIs (index MRI defined as first MRI &amp;gt;1 year post diagnosis). For this preliminary analysis, we include only the 155 patients (70%) who were within 1–3 years of diagnosis at the time of index MRI (see table 1 for patient and disease characteristics). 24/155 (15.5%) screening MRIs were considered not normal. Five women (21%) underwent biopsy based on abnormal MRI finding; 1 resulted in the detection of a local recurrence (4.2%, 95% CI=0.1%–21.1%). 3/131 patients who had a normal index MRI were found to have local/regional recurrence or contralateral breast cancer diagnosed within 2 years of the MRI (2.3%, 95% CI=0.5%–6.6%). A statistically significant difference in the proportions was not observed based on Fisher's test (p = 0.50). 6/155 patients (3.9 %) had a systemic recurrence in the 2 years following index MRI. Conclusion: The vast majority of first screening breast MRIs obtained 1–3 years following treatment in early stage breast cancer survivors are normal, and very few detect cancer. Planned further analysis in this dataset will evaluate frequency of cancer detection in longer-term survivors. Additional research is necessary to determine the risks and benefits of screening breast MRIs being performed in this population. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-09.
Abstract 2645: Genomic deletions and point mutations in the STK11 gene in Peutz-Jeghers Chilean families
Authors: Paulina Orellana, Karin Alvarez, Claudio Heine, Cristobal Suazo, Eliana Pinto, Pilar Carvallo, Francisco López-Kostner
Journal: Cancer Research (2012)

Abstract Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. Individuals with PJS are at increased risk for development of various neoplasms. The genetic susceptibility for PJS has been associated with germline mutation in the serine/threonine kinase 11 (STK11) gene. The aim of the present study was to characterize the genotype and phenotype of Chilean PJS patients. Methods: Mutation screening of 13 patients from 8 PJS families was performed by using single strand conformation polymorphism (SSCP) analysis and DNA sequencing, covering the entire coding region and the splice-site boundaries. In addition, multiplex ligation-dependent probe amplification (MLPA) assay was used for the identification of large exonic deletions or duplications. Results: We identified seven different pathogenic mutations in STK11 gene in 7 unrelated families. Point mutations correspond to a small deletion (c.109delC) in exon 1 that generates a premature stop codon and two intronic mutations localized in splice site of intron 4 (c.597+2 T&amp;gt;A) and intron 6 (c.862-2 A&amp;gt;G). The pathogenic effect on splicing of intronic changes was demonstrated in mRNA of STK11 from lymphocytes of patients. By MLPA, we identified four large deletions ranging from one exon to the whole gene. Breakpoints were identified in two of these patients. Three point mutations (43%, 3/7) may be considered as novel. Conclusions: Different germline mutations in STK11 were detected. A combination of sensitive techniques may improve a high STK11 mutation detection frequency (88%) in PJS Chilean families. Funded by Clinica Las Condes 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 2645. doi:1538-7445.AM2012-2645
NON-INVASIVE ASSESSMENT OF MYOCARDIAL PERFUSION IN ELDERLY MEN: THE IMPACT OF AORTIC STIFFNESS AND CENTRAL BLOOD PRESSURE
Authors: Elizabeth Ellins, Kirsten E. Smith, Lucy T. Lennon, Olia Papacosta, S. Goya Wannamethee, Peter H. Whincup, Julian P. Halcox
Journal: Journal of the American College of Cardiology (2016)
Deterioration of Renal Function after Discontinuation of Long-Term Prednisone-Azathioprine Therapy in Primary Renal Disease
Authors: John I. Levitt
Journal: New England Journal of Medicine (1970)

Three adult patients receiving long-term prednisone-azathioprine therapy for primary renal disease resistant to prednisone alone demonstrated severe abrupt deterioration in renal function when this combined therapy was stopped. The drugs were discontinued after periods of one to three years because continuing proteinuria in all and a slowly falling creatinine clearance in two suggested that they were ineffective. In retrospect it appeared that they were maintaining relative stability of a disease that in their absence became rapidly progressive. Reinstitution of therapy failed to halt the progression in one but reversed it in the other two. Prednisone-azathioprine therapy may alter the progress of renal disease without effecting a noticeable improvement in renal function. This type of latent beneficial response appeared to be occurring in about half our treated cases considered to be resistant to therapy.
Reflex Sympathetic Dystrophy Syndrome Following Air-Bag Inflation
Authors: Nimisha Shah, Arthur Weinstein
Journal: New England Journal of Medicine (1997)

To the Editor: Reflex sympathetic dystrophy syndrome is commonly precipitated by trauma and is characterized by pain and swelling with signs of vasomotor instability in a distal extremity.1 We describe a case of air-bag–induced trauma followed by the reflex sympathetic dystrophy syndrome. A 44-year-old woman had an accident while driving in December 1996. When the air bag inflated, her left and right hands, which were initially on the steering wheel, were pushed back against the window and the seat, respectively. Both carpometacarpal joints were dislocated, causing severe pain. After closed reduction, casts were applied for four weeks. Although the right . . .
Opportunities “Opening Up” For Gene Therapy
Authors: Cori Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Opportunities “Opening Up” For Gene Therapy 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 85, Issue 2, 20 January 1993, Page 90, https://doi.org/10.1093/jnci/85.2.90 Published: 20 January 1993
The problem with ultra-endurance athletes
Authors: George Wortley, Arthur A Islas
Journal: British Journal of Sports Medicine (2011)

Ultra-endurance competitions are defined as events that exceed 6 h.1 These long and gruelling athletic endeavours to most of us are of herculean proportions. For example, ultra-distance running is defined as an activity covering distances greater than a marathon. These include events of 50 km to 100 miles and beyond. Last year in the USA, it was estimated that 10 000 individuals competed in ultra-distance events.2 So what is the problem with ultra-endurance athletes?

The problem is that we, as healthcare providers, do not understand these athletes and they do not understand us. Frequently they come to our office seeking care and advice for an injury that occurred at mile 87 of a 100-mile event, our answer is “Do not do that again”. In doing so we fail to recognise that, specifically for ultra-endurance athletes, the mental fortitude and commitment to their sports is immense and that these athletes …
MORTALITY, EXPENSE AND LENGTH OF STAY WITH LOCAL VERSUS SYSTEMIC THROMBOLYSIS IN PULMONARY EMBOLISM: AN ANALYSIS OF FIVE YEARS OF THE NATIONWIDE INPATIENT SAMPLE DATABASE
Authors: Saurav Chatterjee, Partha Sardar, Sahil Parikh, Anjali Vaidya, Anasua Chakraborty, Debabrata Mukherjee, Jay Giri
Journal: Journal of the American College of Cardiology (2015)